Oral submucous fibrosis is a pre-malignant disorder caused by habitual areca nut consumption. This pilot study investigated the therapeutic potential of dental pulp mesenchymal stem cell-secretome chitosan gel in a mice model of areca nut extract-induced oral submucous fibrosis.
Materials and Methods
Angiogenic potential of dental pulp mesenchymal stem cell-secretome was validated using a chick yolk sac membrane assay. Oral submucous fibrosis was induced in male Swiss albino mice (n = 40) via intraoral areca nut extract administration for 3 months. Post-induction, animals were divided into disease control, DPMSCs-S, and DPMSCs-S gel groups. Treatments were administered intraorally twice weekly for 1 month. Therapeutic efficacy was assessed through measurements of mouth opening, histopathology, oxidative stress markers (LDH, MDA, SOD), and fibrotic gene expression (COL1, COL3, α-SMA).
Results
Dental pulp mesenchymal stem cells’ secretome contains pro-angiogenic growth factors. Dental pulp mesenchymal stem cells’ secretome gel significantly improved mouth opening, restored epithelial architecture, and reduced collagen deposition. Histological staining and gene expression analyses confirmed the reversal of fibrosis and downregulation of COL1, COL3, and α-SMA. Additionally, the gel reduced LDH and MDA levels and enhanced SOD activity, indicating antioxidant effects. The gel showed superior efficacy over the secretome alone.
Conclusion
DPMSCs-S gel demonstrates significant anti-fibrotic, antioxidant, and regenerative potential in reversing ANE-induced OSMF in mice. These findings warrant further investigation into larger, long-term preclinical studies.
{"title":"Dental Pulp Mesenchymal Stem Cell-Secretome Gel Reverse Areca Nut Induced Oral Submucous Fibrosis in Mice: A Pilot Study","authors":"Nishant Mante, Supriya Kheur, Avinash Sanap, Avinash Kharat, Pranjali Potdar, Poonam Suryawanshi, Ravindra Badhe, Vaishali Undale, Nitika Monga, Ramesh Bhonde","doi":"10.1111/jop.70064","DOIUrl":"10.1111/jop.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Oral submucous fibrosis is a pre-malignant disorder caused by habitual areca nut consumption. This pilot study investigated the therapeutic potential of dental pulp mesenchymal stem cell-secretome chitosan gel in a mice model of areca nut extract-induced oral submucous fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Angiogenic potential of dental pulp mesenchymal stem cell-secretome was validated using a chick yolk sac membrane assay. Oral submucous fibrosis was induced in male Swiss albino mice (<i>n</i> = 40) via intraoral areca nut extract administration for 3 months. Post-induction, animals were divided into disease control, DPMSCs-S, and DPMSCs-S gel groups. Treatments were administered intraorally twice weekly for 1 month. Therapeutic efficacy was assessed through measurements of mouth opening, histopathology, oxidative stress markers (LDH, MDA, SOD), and fibrotic gene expression (COL1, COL3, α-SMA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dental pulp mesenchymal stem cells’ secretome contains pro-angiogenic growth factors. Dental pulp mesenchymal stem cells’ secretome gel significantly improved mouth opening, restored epithelial architecture, and reduced collagen deposition. Histological staining and gene expression analyses confirmed the reversal of fibrosis and downregulation of COL1, COL3, and α-SMA. Additionally, the gel reduced LDH and MDA levels and enhanced SOD activity, indicating antioxidant effects. The gel showed superior efficacy over the secretome alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DPMSCs-S gel demonstrates significant anti-fibrotic, antioxidant, and regenerative potential in reversing ANE-induced OSMF in mice. These findings warrant further investigation into larger, long-term preclinical studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"161-167"},"PeriodicalIF":2.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pâmella de Pinho Montovani, Gabriela Pizão Werneck Moreira da Costa, Rafaela Elvira Rozza-de-Menezes, Karin Soares Cunha
Objective
The aim of this study was to determine the prevalence of oral alterations detectable through physical examination in NF1 individuals. Additionally, we assessed the correlation between the number of oral and cutaneous neurofibromas.
Design
This retrospective study evaluated oral alterations in individuals with and without NF1. In the NF1 group, associations between oral and cutaneous neurofibromas, age, sex, pregnancy, and family history of NF1 were assessed.
Results
A total of 327 participants were evaluated (81 with NF1 and 246 controls). Oral mucosal alterations (92.6% vs. 79.3%) and exostoses (12.3% vs. 4.5%) were significantly more prevalent in the NF1 group. The most frequent oral alterations were enlarged fungiform papillae (46.9% vs. 8.1%), coated tongue (45.7% vs. 29.3%), neurofibromas (38.3% versus none), physiological melanin pigmentation (30.9% vs. 10.6%), and exostoses (12.3% vs. 4.5%). Oral neurofibromas were more prevalent in older individuals, without a family history of NF1, and those with multiple cutaneous neurofibromas.
Conclusions
Enlarged fungiform papillae and oral neurofibromas are the most common oral alterations detectable through physical examination in NF1. Coated tongue, physiological melanin pigmentation, and exostoses were also more frequent in NF1. The number of oral and cutaneous neurofibromas is correlated. These findings underscore the necessity of regular oral assessments in NF1 individuals.
目的：本研究的目的是确定NF1个体通过体检可检测到的口腔改变的患病率。此外，我们评估了口腔和皮肤神经纤维瘤数量之间的相关性。设计：本回顾性研究评估了NF1患者和非NF1患者的口腔改变。在NF1组中，评估了口腔和皮肤神经纤维瘤、年龄、性别、妊娠和NF1家族史之间的关系。结果：共有327名参与者被评估（81名NF1患者和246名对照组）。口腔黏膜改变（92.6% vs. 79.3%）和外露（12.3% vs. 4.5%）在NF1组中更为普遍。最常见的口腔病变是真菌状乳头肿大（46.9%比8.1%）、舌膜覆盖（45.7%比29.3%）、神经纤维瘤（38.3%比无）、生理性黑色素沉着（30.9%比10.6%）和外生瘤（12.3%比4.5%）。口腔神经纤维瘤在没有NF1家族史的老年人和多发性皮肤神经纤维瘤患者中更为普遍。结论：真菌状乳头状瘤和口腔神经纤维瘤是NF1患者体格检查中最常见的口腔病变。舌包膜、生理性黑色素沉着和外生骨瘤在NF1中也更为常见。口腔和皮肤神经纤维瘤的数量是相关的。这些发现强调了对NF1个体进行定期口腔评估的必要性。
{"title":"Prevalence of Oral Alterations and Correlation Between Oral and Cutaneous Neurofibromas in Neurofibromatosis Type 1: A Retrospective Case–Control Study","authors":"Pâmella de Pinho Montovani, Gabriela Pizão Werneck Moreira da Costa, Rafaela Elvira Rozza-de-Menezes, Karin Soares Cunha","doi":"10.1111/jop.70056","DOIUrl":"10.1111/jop.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to determine the prevalence of oral alterations detectable through physical examination in NF1 individuals. Additionally, we assessed the correlation between the number of oral and cutaneous neurofibromas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>This retrospective study evaluated oral alterations in individuals with and without NF1. In the NF1 group, associations between oral and cutaneous neurofibromas, age, sex, pregnancy, and family history of NF1 were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 327 participants were evaluated (81 with NF1 and 246 controls). Oral mucosal alterations (92.6% vs. 79.3%) and exostoses (12.3% vs. 4.5%) were significantly more prevalent in the NF1 group. The most frequent oral alterations were enlarged fungiform papillae (46.9% vs. 8.1%), coated tongue (45.7% vs. 29.3%), neurofibromas (38.3% versus none), physiological melanin pigmentation (30.9% vs. 10.6%), and exostoses (12.3% vs. 4.5%). Oral neurofibromas were more prevalent in older individuals, without a family history of NF1, and those with multiple cutaneous neurofibromas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Enlarged fungiform papillae and oral neurofibromas are the most common oral alterations detectable through physical examination in NF1. Coated tongue, physiological melanin pigmentation, and exostoses were also more frequent in NF1. The number of oral and cutaneous neurofibromas is correlated. These findings underscore the necessity of regular oral assessments in NF1 individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"155-160"},"PeriodicalIF":2.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
16-hydroxycleroda-3,13-dien-15,16-olide (HCD), a compound isolated from Polyalthia longifolia var. pendula, has been identified as a PI3K inhibitor. P. longifolia var. pendula is recognized for its diverse pharmacological properties, including antimicrobial, hypotensive, anti-inflammatory, and cytotoxic activities. Considering the pivotal role of PI3K in the regulation of apoptosis in cancer cells, this study aims to investigate the apoptotic effects induced by HCD in head and neck cancer cell models.
Methods
The study focused on investigating the mechanism through which HCD induces apoptosis in oral squamous cell carcinoma (OSCC) using SCC25 and SCC180 cells. These cells were treated with HCD at IC20, IC50, and IC80 concentrations over periods of 24, 48, and 72 h. Assessments included cell viability, oxidative stress levels using MitoSOX and CellROX, and the analysis of gene and protein expressions related to apoptosis via immunofluorescence staining, flow cytometry, RT-PCR, and western blotting.
Results
The results demonstrated that HCD significantly increased the sub-G1 phase cell population, suppressed clonogenic activity, and promoted mitochondrial ROS production, accompanied by a reduction in glutathione levels. HCD also activated cytochrome c (cyto. c) release and Bax expression while downregulating Bcl-2 expression. Notably, in SCC25 cells, HCD induced apoptosis through the TNF-α/TNF-R and FasL/Fas death domains, leading to caspase cascade activation. Moreover, HCD showed dose-dependent growth inhibition of SCC25 cells, both alone and combined with cisplatin, by enhancing caspase-3 expression.
Conclusion
This investigation into HCD's molecular mechanisms in OSCC cells offers insight into developing effective anticancer therapies, highlighting its role in apoptosis induction through oxidative stress, mitochondrial pathways, and death receptor signaling.
{"title":"The PI3K Inhibitor HCD Promotes Caspase Activation in Head and Neck Squamous Cells by Upregulating the Extrinsic and Intrinsic Apoptosis Pathways","authors":"Leong-Perng Chan, Ya-Ping Tseng, Hui-Ching Wang, Chen-Yu Chien, Che-Wei Wu, Ling-Feng Wang, Tung-Wen Yen, Po-Chun Wang, Chih-Chuang Liaw, Chia-Hua Liang","doi":"10.1111/jop.70060","DOIUrl":"10.1111/jop.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>16-hydroxycleroda-3,13-dien-15,16-olide (HCD), a compound isolated from <i>Polyalthia longifolia</i> var. <i>pendula</i>, has been identified as a PI3K inhibitor. <i>\u0000 P. longifolia var. pendula</i> is recognized for its diverse pharmacological properties, including antimicrobial, hypotensive, anti-inflammatory, and cytotoxic activities. Considering the pivotal role of PI3K in the regulation of apoptosis in cancer cells, this study aims to investigate the apoptotic effects induced by HCD in head and neck cancer cell models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study focused on investigating the mechanism through which HCD induces apoptosis in oral squamous cell carcinoma (OSCC) using SCC25 and SCC180 cells. These cells were treated with HCD at IC<sub>20</sub>, IC<sub>50</sub>, and IC<sub>80</sub> concentrations over periods of 24, 48, and 72 h. Assessments included cell viability, oxidative stress levels using MitoSOX and CellROX, and the analysis of gene and protein expressions related to apoptosis via immunofluorescence staining, flow cytometry, RT-PCR, and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrated that HCD significantly increased the sub-G<sub>1</sub> phase cell population, suppressed clonogenic activity, and promoted mitochondrial ROS production, accompanied by a reduction in glutathione levels. HCD also activated cytochrome <i>c</i> (cyto. <i>c</i>) release and Bax expression while downregulating Bcl-2 expression. Notably, in SCC25 cells, HCD induced apoptosis through the TNF-α/TNF-R and FasL/Fas death domains, leading to caspase cascade activation. Moreover, HCD showed dose-dependent growth inhibition of SCC25 cells, both alone and combined with cisplatin, by enhancing caspase-3 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This investigation into HCD's molecular mechanisms in OSCC cells offers insight into developing effective anticancer therapies, highlighting its role in apoptosis induction through oxidative stress, mitochondrial pathways, and death receptor signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"61-72"},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruno Romano de Oliveira, Warley Oliveira Silva, Carolina Cavaliéri Gomes, Jean Nunes dos Santos, Fabrício Tinôco Alvim de Souza
Background
Polymorphous adenocarcinoma (PmA) is the second most common malignant neoplasm in minor salivary glands; a subtype of this lesion was described in 2005 with more aggressive behavior, Cribriform Adenocarcinoma of Salivary Glands (CASG).
Objective
To compare the clinical aspects of conventional PmA and CASG originating in minor salivary glands of the oral cavity through the analysis of observational studies reported in the literature between 2005 and 2025.
Method
This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The review included searches of Pubmed, Lilacs, Scopus, and Web of Science databases. A total of 988 records were identified, and after the selection process, 47 articles were chosen for inclusion.
Results
Females were the most affected (61% in PmA and 73.3% in CASG). The average age variation was 60 in PmA and 57.3 in CASG. The most frequent anatomical location was the palate (42.4%) in PmA and the tongue (46.7%) in CASG. Lymph node metastasis was found in 15.2% in PmA and in 60% in CASG. The most commonly used treatment was surgical excision (72.72%) in PmA and surgical excision and neck dissection (46.67%) in CASG. Recurrence rates were 9.09% in PmA and 33.33% in CASG. The average follow-up period was 21.7 months in PmA and 43.9 in CASG.
Conclusion
Female predilection and average age of 60 years are common between the two tumors. The clinical variables with quantitative differences are anatomical location, lymph node metastasis, treatment modality, and recurrence.
背景：多形态腺癌（PmA）是小唾液腺第二常见的恶性肿瘤；这种病变的一个亚型在2005年被描述为更具侵略性的行为，即唾液腺筛状腺癌（CASG）。目的：通过对2005年至2025年文献报道的观察性研究进行分析，比较传统PmA和起源于口腔小涎腺的CASG的临床特点。方法：本系统评价遵循系统评价和荟萃分析（PRISMA）指南的首选报告项目。该综述包括Pubmed、Lilacs、Scopus和Web of Science数据库的搜索。共确定了988条记录，经过筛选过程，选择了47篇文章纳入。结果：女性受影响最大（PmA为61%，CASG为73.3%）。PmA的平均年龄变化为60，CASG的平均年龄变化为57.3。最常见的解剖位置为上颚（42.4%）和舌部（46.7%）。PmA和CASG的淋巴结转移率分别为15.2%和60%。PmA最常用的治疗方法是手术切除（72.72%），CASG最常用的治疗方法是手术切除加颈部清扫（46.67%）。PmA复发率为9.09%，CASG为33.33%。PmA组平均随访21.7个月，CASG组平均随访43.9个月。结论：两种肿瘤均以女性为主，平均年龄60岁。具有数量差异的临床变量为解剖位置、淋巴结转移、治疗方式和复发。
{"title":"A Comparative Analysis of Clinical Aspects of Conventional Polymorphous Adenocarcinoma and Cribriform Adenocarcinoma of Salivary Glands: A Systematic Review","authors":"Bruno Romano de Oliveira, Warley Oliveira Silva, Carolina Cavaliéri Gomes, Jean Nunes dos Santos, Fabrício Tinôco Alvim de Souza","doi":"10.1111/jop.70067","DOIUrl":"10.1111/jop.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Polymorphous adenocarcinoma (PmA) is the second most common malignant neoplasm in minor salivary glands; a subtype of this lesion was described in 2005 with more aggressive behavior, Cribriform Adenocarcinoma of Salivary Glands (CASG).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the clinical aspects of conventional PmA and CASG originating in minor salivary glands of the oral cavity through the analysis of observational studies reported in the literature between 2005 and 2025.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The review included searches of Pubmed, Lilacs, Scopus, and Web of Science databases. A total of 988 records were identified, and after the selection process, 47 articles were chosen for inclusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Females were the most affected (61% in PmA and 73.3% in CASG). The average age variation was 60 in PmA and 57.3 in CASG. The most frequent anatomical location was the palate (42.4%) in PmA and the tongue (46.7%) in CASG. Lymph node metastasis was found in 15.2% in PmA and in 60% in CASG. The most commonly used treatment was surgical excision (72.72%) in PmA and surgical excision and neck dissection (46.67%) in CASG. Recurrence rates were 9.09% in PmA and 33.33% in CASG. The average follow-up period was 21.7 months in PmA and 43.9 in CASG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Female predilection and average age of 60 years are common between the two tumors. The clinical variables with quantitative differences are anatomical location, lymph node metastasis, treatment modality, and recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"23-31"},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Divya Gopinath, Cheng Yung On, Chathathayil Mohammedali Shafeeque, Sajesh K. Veettil, Wanninayake M. Tilakaratne
Background
Varied susceptibility to Oral submucous fibrosis (OSF) among individuals exposed to the same environmental variables indicates that genetic variation may contribute as a risk factor in its development. The objective was to comprehensively analyze the association between single gene polymorphisms (SNPs) and the risk of OSF.
Methods
This comprehensive systematic review encompassed all relevant published studies up until June 2024 that examined the influence of gene polymorphisms on the likelihood of OSF. The search was conducted across multiple databases, including Medline, Scopus, and EBSCOhost. Data were pooled in a random-effect meta-analysis where at least two studies on the same SNP tested the same genotyping model. The assessment of heterogeneity was conducted using the I2 statistic. The Q-Genie tool was used to evaluate the quality of the included studies.
Results
Out of the 4573 papers initially searched, only 37 articles met the criteria to be included in this review. A total of 63 SNPs from 27 genes were tested, and 38 SNPs had significant associations. The meta-analysis revealed that five SNPs, including GSTM1 null (OR = 1.90; 1.41–2.56), GSTT1 null (OR = 2.41; 1.64–3.53), MMP3 (−1171; promoter region) (OR = 3.33; 1.45–7.61), XXCR3 (T vs. C) (OR = 1.70 (1.23–2.36)) and CYP1A1 m2 at Ncol site (−) (OR = 4.32; 1.22–15.29), are associated with an increased risk of OSF.
Conclusion
The limited SNPs identified in this review could be used as markers to identify patients at a higher risk of OSF. Further studies are warranted to validate the SNPs, which demonstrate contradictory results among the currently available studies.
{"title":"Single Nucleotide Polymorphisms as Markers of Genetic Susceptibility for Oral Submucous Fibrosis Risk: A Systematic Review and Meta-Analysis","authors":"Divya Gopinath, Cheng Yung On, Chathathayil Mohammedali Shafeeque, Sajesh K. Veettil, Wanninayake M. Tilakaratne","doi":"10.1111/jop.70054","DOIUrl":"10.1111/jop.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Varied susceptibility to Oral submucous fibrosis (OSF) among individuals exposed to the same environmental variables indicates that genetic variation may contribute as a risk factor in its development. The objective was to comprehensively analyze the association between single gene polymorphisms (SNPs) and the risk of OSF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This comprehensive systematic review encompassed all relevant published studies up until June 2024 that examined the influence of gene polymorphisms on the likelihood of OSF. The search was conducted across multiple databases, including Medline, Scopus, and EBSCOhost. Data were pooled in a random-effect meta-analysis where at least two studies on the same SNP tested the same genotyping model. The assessment of heterogeneity was conducted using the <i>I</i>\u0000 <sup>2</sup> statistic. The Q-Genie tool was used to evaluate the quality of the included studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of the 4573 papers initially searched, only 37 articles met the criteria to be included in this review. A total of 63 SNPs from 27 genes were tested, and 38 SNPs had significant associations. The meta-analysis revealed that five SNPs, including GSTM1 null (OR = 1.90; 1.41–2.56), GSTT1 null (OR = 2.41; 1.64–3.53), MMP3 (−1171; promoter region) (OR = 3.33; 1.45–7.61), XXCR3 (T vs. C) (OR = 1.70 (1.23–2.36)) and CYP1A1 m2 at Ncol site (−) (OR = 4.32; 1.22–15.29), are associated with an increased risk of OSF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The limited SNPs identified in this review could be used as markers to identify patients at a higher risk of OSF. Further studies are warranted to validate the SNPs, which demonstrate contradictory results among the currently available studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"7-22"},"PeriodicalIF":2.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Widespread legalizations of cannabis in many states also cause increased interest in the adverse effects of its use, including increased risk for head and neck cancer.
Methods and Results
To test the hypothesis that cannabis increases the risk for head and neck cancers, we have used the i2b2 platform and ICD 10 codes to access a large Hospital database and identify patients with head and neck cancer and patients who were cannabis users. Binary Logistic regression of factors such as demographics, smoking, alcohol consumption, and HPV vaccine history was used. The odds ratio for oropharyngeal cancer among cannabis users was 3.12. After logistic regressions, it remained significant after adjusting for gender, age, and race but became insignificant after adjusting for alcohol, cigarette smoking, and HPV vaccine (1.07, 0.87, 1.02), respectively. The odds ratio for oral cancer among cannabis users was 2.38 before adjustments. It remained significant after adjustment for gender, age, race, and HPV vaccine but became insignificant after adjustment for alcohol and cigarette smoking (0.7, 0.62). After adjusting for cannabis use, the odds ratio for oropharyngeal cancer in the alcohol users was 7.95 and 7.39 for smokers. The odds ratio for oral cancer after adjusting for cannabis in the alcohol users was 9.67 and 7.52 in the cigarette smokers. HPV vaccination had an inhibitory effect on both cancers.
Conclusions
Alcohol and cigarette smoking rather than the use of cannabis may play a major role in establishing an association between cannabis use and both types of head and neck cancers.
{"title":"Use of Cannabis and Odds Ratio for Oropharyngeal and Oral Cancer—A Cohort Study","authors":"J. Katz, H. Gao, S. Spritzer, I. A. Garcia","doi":"10.1111/jop.70055","DOIUrl":"10.1111/jop.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Widespread legalizations of cannabis in many states also cause increased interest in the adverse effects of its use, including increased risk for head and neck cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>To test the hypothesis that cannabis increases the risk for head and neck cancers, we have used the i2b2 platform and ICD 10 codes to access a large Hospital database and identify patients with head and neck cancer and patients who were cannabis users. Binary Logistic regression of factors such as demographics, smoking, alcohol consumption, and HPV vaccine history was used. The odds ratio for oropharyngeal cancer among cannabis users was 3.12. After logistic regressions, it remained significant after adjusting for gender, age, and race but became insignificant after adjusting for alcohol, cigarette smoking, and HPV vaccine (1.07, 0.87, 1.02), respectively. The odds ratio for oral cancer among cannabis users was 2.38 before adjustments. It remained significant after adjustment for gender, age, race, and HPV vaccine but became insignificant after adjustment for alcohol and cigarette smoking (0.7, 0.62). After adjusting for cannabis use, the odds ratio for oropharyngeal cancer in the alcohol users was 7.95 and 7.39 for smokers. The odds ratio for oral cancer after adjusting for cannabis in the alcohol users was 9.67 and 7.52 in the cigarette smokers. HPV vaccination had an inhibitory effect on both cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Alcohol and cigarette smoking rather than the use of cannabis may play a major role in establishing an association between cannabis use and both types of head and neck cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"147-151"},"PeriodicalIF":2.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fernando Costa Giffoni, Thaís Ellen Chaves Gomes, Priscila Nazaré de Souza, Paula Valente e Silva, Luiz Alexandre Viana Magno, Amanda Lage Cândido, Marcelo Faria Lasmar, Sebastião Guilherme de Oliveira Neto, Marcus Vinicius Lucas Ferreira, Thiago Moreira Gonçalves Araujo, Luara Isabela dos Santos, Bruno Ramos Chrcanovic, Ricardo Santiago Gomez, Roberta Rayra Martins-Chaves
Background
The biological effects of dental implants on peri-implant tissues have been widely investigated. Recent reports of oral squamous cell carcinoma (OSCC) cases adjacent to dental implants have raised concerns regarding the potential impact of implant materials on cellular aging and oncogenic transformation. Telomeres, which protect chromosome ends, undergo progressive shortening and play a critical role in cellular senescence and tumorigenesis. However, the impact of dental implants on telomere length in peri-implant mucosa remains unclear.
Objective
This study aimed to compare telomere length in mucosa adjacent to dental implants with that of gingival tissue associated with healthy teeth.
Methods
A paired cross-sectional study was conducted with 16 patients who had dental implants for at least 1 year. Swabs were collected from the peri-implant mucosa and healthy gingival mucosa of the same patient. Telomere length was assessed using quantitative PCR, with the relative telomere-to-single-copy-gene ratio (T/C) calculated using the 2−∆∆Cq method.
Results
Telomere length in the peri-implant mucosa was not significantly different from that in the healthy gingival mucosa (p = 0.117).
Conclusion
These findings suggest that dental implants do not alter telomere length in adjacent mucosal cells.
{"title":"Investigation of the Telomere Length in PERI-Implant Oral Mucosa Cells","authors":"Fernando Costa Giffoni, Thaís Ellen Chaves Gomes, Priscila Nazaré de Souza, Paula Valente e Silva, Luiz Alexandre Viana Magno, Amanda Lage Cândido, Marcelo Faria Lasmar, Sebastião Guilherme de Oliveira Neto, Marcus Vinicius Lucas Ferreira, Thiago Moreira Gonçalves Araujo, Luara Isabela dos Santos, Bruno Ramos Chrcanovic, Ricardo Santiago Gomez, Roberta Rayra Martins-Chaves","doi":"10.1111/jop.70061","DOIUrl":"10.1111/jop.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The biological effects of dental implants on peri-implant tissues have been widely investigated. Recent reports of oral squamous cell carcinoma (OSCC) cases adjacent to dental implants have raised concerns regarding the potential impact of implant materials on cellular aging and oncogenic transformation. Telomeres, which protect chromosome ends, undergo progressive shortening and play a critical role in cellular senescence and tumorigenesis. However, the impact of dental implants on telomere length in peri-implant mucosa remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to compare telomere length in mucosa adjacent to dental implants with that of gingival tissue associated with healthy teeth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A paired cross-sectional study was conducted with 16 patients who had dental implants for at least 1 year. Swabs were collected from the peri-implant mucosa and healthy gingival mucosa of the same patient. Telomere length was assessed using quantitative PCR, with the relative telomere-to-single-copy-gene ratio (T/C) calculated using the 2<sup>−∆∆Cq</sup> method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Telomere length in the peri-implant mucosa was not significantly different from that in the healthy gingival mucosa (<i>p</i> = 0.117).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that dental implants do not alter telomere length in adjacent mucosal cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"152-154"},"PeriodicalIF":2.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah Gil de Farias Morais, Débora Frota Colares, Maurília Raquel de Souto Medeiros, Caio César da Silva Barros, Everton Freitas de Morais, Márcia Cristina da Costa Miguel, Roseana de Almeida Freitas
Background
Fibro-osseous lesions (FOL) of the jawbones and cemento-ossifying fibroma (COF) represent a heterogeneous group of lesions with overlapping histopathological features and variability in biological behavior. Thus, this study aimed to evaluate the clinical, radiographic, and histopathological characteristics of FOLs (cemento-osseous dysplasia—COD, fibrous dysplasia—FD, ossifying fibroma—OF) as well as COF, diagnosed at a reference center in oral pathology over 53 years.
Methods
Sex, age, symptoms, clinical diagnosis, time of evolution, anatomical site, size of the lesion, and radiographic characteristics were collected from all cases of lesions previously diagnosed as FOLs.
Results
Among 19 600 cases of oral and maxillofacial lesions diagnosed at our center, 156 (0.8%) had a histological diagnosis of FOL, with COD being the most common (37.2%). Radiographically, most cases presented as unilocular lesions (64.3%) (p = 0.034) with mixed radiolucency (53.8%). COD and COF frequently exhibited well-defined borders. Additionally, 50% of COD cases displayed a cotton-wool appearance, while half of FDs appeared as ground-glass opacifications. Histopathologically, a significantly high frequency of lamellar bone was observed in all types of FOL (p = 0.0001). In contrast, peritrabecular clefting was significantly found in FDs, and cementum-like tissue in CODs and COFs (p < 0.05). Lesional bone fusing with the normal adjacent bone was more significantly observed in COD and FD (p = 0.001).
Conclusion
A definitive and accurate diagnosis of FOL is achievable when cases are individually investigated, and all clinical, radiographic, and histopathologic features are analyzed.
{"title":"Clinical, Radiographic and Histopathological Analysis of Cemento-Ossifying Fibromas and Fibro-Osseous Lesions of the Oral and Maxillofacial Region: A 53-Year Retrospective Study and Update of Current Concepts","authors":"Hannah Gil de Farias Morais, Débora Frota Colares, Maurília Raquel de Souto Medeiros, Caio César da Silva Barros, Everton Freitas de Morais, Márcia Cristina da Costa Miguel, Roseana de Almeida Freitas","doi":"10.1111/jop.70059","DOIUrl":"10.1111/jop.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fibro-osseous lesions (FOL) of the jawbones and cemento-ossifying fibroma (COF) represent a heterogeneous group of lesions with overlapping histopathological features and variability in biological behavior. Thus, this study aimed to evaluate the clinical, radiographic, and histopathological characteristics of FOLs (cemento-osseous dysplasia—COD, fibrous dysplasia—FD, ossifying fibroma—OF) as well as COF, diagnosed at a reference center in oral pathology over 53 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sex, age, symptoms, clinical diagnosis, time of evolution, anatomical site, size of the lesion, and radiographic characteristics were collected from all cases of lesions previously diagnosed as FOLs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 19 600 cases of oral and maxillofacial lesions diagnosed at our center, 156 (0.8%) had a histological diagnosis of FOL, with COD being the most common (37.2%). Radiographically, most cases presented as unilocular lesions (64.3%) (<i>p</i> = 0.034) with mixed radiolucency (53.8%). COD and COF frequently exhibited well-defined borders. Additionally, 50% of COD cases displayed a cotton-wool appearance, while half of FDs appeared as ground-glass opacifications. Histopathologically, a significantly high frequency of lamellar bone was observed in all types of FOL (<i>p</i> = 0.0001). In contrast, peritrabecular clefting was significantly found in FDs, and cementum-like tissue in CODs and COFs (<i>p</i> < 0.05). Lesional bone fusing with the normal adjacent bone was more significantly observed in COD and FD (<i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A definitive and accurate diagnosis of FOL is achievable when cases are individually investigated, and all clinical, radiographic, and histopathologic features are analyzed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 10","pages":"1062-1073"},"PeriodicalIF":2.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wender Rodrigues Nazário, Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira Santos, Nayara Rúbio Diniz Del Nero, Tamiris Sabrina Rodrigues, Luiza Diniz Ferreira Borges, Carlos Ueira-Vieira, Sérgio Vitorino Cardoso, Adriano Mota Loyola, Paulo Rogério de Faria
Background
Oral squamous cell carcinoma (OSCC) is one of the most frequent head and neck cancers. The 4-nitroquinoline 1-oxide (4NQO) mouse model of oral carcinogenesis is a well-established model to investigate the mechanism behind OSCC development, including epigenetic alterations. Studies have shown that histone acetylation is a key regulator of gene expression and may play a role in such a tumor. This study investigates the acetylation of H3K9, H3K14, and H3K27 and the KAT2A gene expression in a sex-based approach in a 4NQO/ethanol (EtOH)-induced OSCC mouse model.
Methods
A total of 120 C57Bl/6J mice (60 males and 60 females) were divided into four groups (n = 15). In the first 10 weeks, they were treated with 5 mg/mL propylene glycol (PPG) or 100 μg/mL 4NQO in drinking water, followed by either sterilized water or 8% EtOH for 15 weeks. After euthanasia, tongues were analyzed histopathologically. Immunohistochemistry and qPCR were also employed to study the histones and gene expression.
Results
Female mice showed increased H3K9ac and H3K14ac expression from normal mucosa to dysplasia, followed by decreased expression in OSCC. H3K9ac and H3K14ac expression in males was lower in the 4NQO/EtOH group. H3K27ac was higher in dysplastic lesions compared to OSCC, particularly in females. Comparatively, females had higher H3K9ac and H3K14ac expression in the 4NQO/EtOH group than males. KAT2A expression was lower in females treated with PPG/EtOH and 4NQO/H2O than in males.
Conclusion
Our results indicate that H3 acetylation and KAT2A gene expression may play a key role in oral carcinogenesis on a sex-related basis.
{"title":"Sex-Related Differences in Histone Acetylation and Tumor Development in a 4-Nitroquinoline 1-Oxide and Ethanol-Induced Oral Squamous Cell Carcinoma Mouse Model","authors":"Wender Rodrigues Nazário, Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira Santos, Nayara Rúbio Diniz Del Nero, Tamiris Sabrina Rodrigues, Luiza Diniz Ferreira Borges, Carlos Ueira-Vieira, Sérgio Vitorino Cardoso, Adriano Mota Loyola, Paulo Rogério de Faria","doi":"10.1111/jop.70062","DOIUrl":"10.1111/jop.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral squamous cell carcinoma (OSCC) is one of the most frequent head and neck cancers. The 4-nitroquinoline 1-oxide (4NQO) mouse model of oral carcinogenesis is a well-established model to investigate the mechanism behind OSCC development, including epigenetic alterations. Studies have shown that histone acetylation is a key regulator of gene expression and may play a role in such a tumor. This study investigates the acetylation of H3K9, H3K14, and H3K27 and the <i>KAT2A</i> gene expression in a sex-based approach in a 4NQO/ethanol (EtOH)-induced OSCC mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 120 C57Bl/6J mice (60 males and 60 females) were divided into four groups (<i>n</i> = 15). In the first 10 weeks, they were treated with 5 mg/mL propylene glycol (PPG) or 100 μg/mL 4NQO in drinking water, followed by either sterilized water or 8% EtOH for 15 weeks. After euthanasia, tongues were analyzed histopathologically. Immunohistochemistry and qPCR were also employed to study the histones and gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Female mice showed increased H3K9ac and H3K14ac expression from normal mucosa to dysplasia, followed by decreased expression in OSCC. H3K9ac and H3K14ac expression in males was lower in the 4NQO/EtOH group. H3K27ac was higher in dysplastic lesions compared to OSCC, particularly in females. Comparatively, females had higher H3K9ac and H3K14ac expression in the 4NQO/EtOH group than males. <i>KAT2A</i> expression was lower in females treated with PPG/EtOH and 4NQO/H<sub>2</sub>O than in males.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicate that H3 acetylation and <i>KAT2A</i> gene expression may play a key role in oral carcinogenesis on a sex-related basis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 10","pages":"1074-1084"},"PeriodicalIF":2.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dandara Andrade De Santana, Cecília Vitória Lima De Oliveira, Flávia Caló De Aquino Xavier, Manoela Domingues Martins, Bruno Cunha Pires, Tercio Guimarães Reis, Patrícia Ramos Cury, Clarissa Araújo Gurgel, Maria Cristina Teixeira Cangussu, Daniel Araki Ribeiro, Victor Coutinho Bastos, Carolina Cavalieri Gomes, Jean Nunes Dos Santos
Purpose
Polymorphous adenocarcinoma of the salivary gland is characterized by cellular uniformity associated with a variety of morphological growth patterns, a fact that makes its diagnosis challenging. Therefore, the identification of genetic alterations and signaling pathways emerges as a tool for elucidation of the pathogenesis of this tumor and accurate differential diagnosis. The aim of this study was to assess mutations in the PRKD1 gene and in protein components of the HH pathway (SHH, IHH, SMO, and GLI-1) in cases of polymorphous adenocarcinoma of the salivary gland.
Methods
Sanger sequencing was used to interrogate hotspot mutations in PRKD1 exon 15 and immunohistochemistry to analyze the protein expression of PRKD1, SHH, IHH, SMO, and GLI-1.
Results
The PRKD1 c.2130A>C/T hotspot mutation was detected in 50% of the sequenced samples. A previously unreported variant, c.2110C>T resulting in p.His704Tyr, was identified in one case, while 100% of the samples carried the intronic variation rs2273813, regardless of tissue invasion (perineural, lymphovascular, fat, bone, muscle, and mucous acini). Immunostaining revealed significant results for several associations between PRKD1, IHH, SMO, and GLI-1. In contrast, SHH immunoexpression did not correlate with the expression of the other proteins.
Conclusion
The PRKD1 E710D hotspot mutation and protein expression of PRKD1 and HH components (SHH, IHH, SMO, and GLI-1) were detected in PAC regardless of tissue invasion, although HH proteins contributed to the morphogenesis of this rare oral cancer. Additionally, the positive correlation between the expression of PRKD1 and HH pathway components (IHH, SMO, and GLI-1) suggests a possible interaction between these proteins, independent of the HH pathway ligand.
目的：涎腺多形腺癌的特征是细胞均匀性与多种形态生长模式相关，这一事实使其诊断具有挑战性。因此，基因改变和信号通路的识别成为阐明该肿瘤发病机制和准确鉴别诊断的工具。本研究的目的是评估涎腺多形性腺癌病例中PRKD1基因和HH通路蛋白组分（SHH、IHH、SMO和gli1）的突变。方法：采用Sanger测序法查询PRKD1外显子15的热点突变，免疫组化分析PRKD1、SHH、IHH、SMO和gli1的蛋白表达。结果：50%的测序样本检测到PRKD1 C . 2130a >C/T热点突变。在一个病例中发现了一种以前未报道的变异，c.2110C . >T导致p.h as704tyr，而100%的样本携带内含子变异rs2273813，而不考虑组织侵犯（神经周围、淋巴血管、脂肪、骨骼、肌肉和粘液腺泡）。免疫染色显示PRKD1、IHH、SMO和gli1之间存在显著的关联。相反，SHH的免疫表达与其他蛋白的表达无关。结论：尽管HH蛋白参与了这种罕见口腔癌的形态发生，但在PAC中PRKD1 E710D热点突变以及PRKD1和HH组分（SHH、IHH、SMO和gli1）的蛋白表达与组织侵袭无关。此外，PRKD1与HH通路组分（IHH、SMO和gli1）的表达呈正相关，表明这些蛋白之间可能存在相互作用，独立于HH通路配体。
{"title":"Hedgehog Components Are Present in Polymorphous Adenocarcinoma of the Salivary Gland Regardless of PRKD1 Mutation and Tissue Invasion","authors":"Dandara Andrade De Santana, Cecília Vitória Lima De Oliveira, Flávia Caló De Aquino Xavier, Manoela Domingues Martins, Bruno Cunha Pires, Tercio Guimarães Reis, Patrícia Ramos Cury, Clarissa Araújo Gurgel, Maria Cristina Teixeira Cangussu, Daniel Araki Ribeiro, Victor Coutinho Bastos, Carolina Cavalieri Gomes, Jean Nunes Dos Santos","doi":"10.1111/jop.70057","DOIUrl":"10.1111/jop.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Polymorphous adenocarcinoma of the salivary gland is characterized by cellular uniformity associated with a variety of morphological growth patterns, a fact that makes its diagnosis challenging. Therefore, the identification of genetic alterations and signaling pathways emerges as a tool for elucidation of the pathogenesis of this tumor and accurate differential diagnosis. The aim of this study was to assess mutations in the \u0000 <i>PRKD1</i>\u0000 gene and in protein components of the HH pathway (SHH, IHH, SMO, and GLI-1) in cases of polymorphous adenocarcinoma of the salivary gland.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sanger sequencing was used to interrogate hotspot mutations in \u0000 <i>PRKD1</i>\u0000 exon 15 and immunohistochemistry to analyze the protein expression of PRKD1, SHH, IHH, SMO, and GLI-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The \u0000 <i>PRKD1</i>\u0000 c.2130A>C/T hotspot mutation was detected in 50% of the sequenced samples. A previously unreported variant, c.2110C>T resulting in p.His704Tyr, was identified in one case, while 100% of the samples carried the intronic variation rs2273813, regardless of tissue invasion (perineural, lymphovascular, fat, bone, muscle, and mucous acini). Immunostaining revealed significant results for several associations between PRKD1, IHH, SMO, and GLI-1. In contrast, SHH immunoexpression did not correlate with the expression of the other proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The \u0000 <i>PRKD1</i> E710D hotspot mutation and protein expression of PRKD1 and HH components (SHH, IHH, SMO, and GLI-1) were detected in PAC regardless of tissue invasion, although HH proteins contributed to the morphogenesis of this rare oral cancer. Additionally, the positive correlation between the expression of PRKD1 and HH pathway components (IHH, SMO, and GLI-1) suggests a possible interaction between these proteins, independent of the HH pathway ligand.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 10","pages":"1053-1061"},"PeriodicalIF":2.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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