Journal of Oral Pathology & Medicine最新文献

Background: Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway. OKC predominantly occurs in young adults and is mostly asymptomatic at the time of initial diagnosis. As OKC is asymptomatic, GS can be challenging to diagnose in certain instances. In this study, we attempted to identify asymptomatic GS from sporadic OKC cases using a previously developed gene panel for GS.

Methods: Genomic DNA was extracted from patient samples. These DNA samples were analyzed using the AmpliSeq Custom DNA Panel (Illumina), which was specifically designed to target four previously established genes (PTCH1, PTCH2, SMO, and SUFU). Mutations from patients were predicted using tools, such as MutationTaster, CADD, and Polyphen-2.

Results: Thirty-one patients with OKC were included: 22 sporadic, 9 syndromic, 14 cases with dentigerous cysts, and 3 patients with orthokeratinized odontogenic cysts. One patient with sporadic OKC carried 50% genetic mutation in the cyst and blood, indicative of GS. PTCH1 mutations were found in one of the 14 patients with dentigerous cysts, 3 of the 17 first-time sporadic cases, and all four recurrent cases. Resected OKC tissues revealed a PTCH1 mutation.

Conclusions: We found one patient with GS from those diagnosed with sporadic OKC. Our findings suggest that PTCH1 mutations are associated with postoperative recurrence of OKC, implying that hedgehog-related gene variations may contribute to jaw cyst development and improve the prognosis of OKC.

Background: Despite recent advancements, women still encounter significant challenges in various fields, including dentistry. However, the increasing interest in female participation in science acknowledges its fundamental role in the advancement of knowledge. This study aims to assess indicators of women's involvement in Brazilian research in the areas of Oral Pathology and Oral Medicine.

Methods: This cross-sectional study evaluated 197 professionals affiliated with the Brazilian Society of Stomatology and Oral Pathology in 2023. Data were collected from publicly available Lattes curriculum and organized into three sets of information: researcher profile, scientific production and human resources formation. Both the data from the researcher's entire career and from the last 5 years (2019-2023) were assessed separately. Descriptive analyses of categorical variables were performed, while the Mann-Whitney test was employed to compare the numerical variables regarding researchers' gender.

Results: Of 197 professionals, 117 (59.4%) were female. Although there was no significant difference in scientific production between genders, men had more publications, received approximately twice as many citations, and exhibited higher H-index values compared to women. Notably, women surpassed men in undergraduate student supervision, while men predominated in supervising master's and PhD students.

Conclusions: This study highlighted the relevance of female participation in Oral Pathology and Oral Medicine research in Brazil. However, disparities persist regarding women participation, especially in scientific article citations and postgraduate students' supervision.

Background: There is lack of knowledge on the utility of prognostic histopathologic characteristics in adenoid cystic carcinoma (ACC) of the head and neck. We evaluated the prognostic value of tumor and stroma-related histopathologic features in ACC.

Materials and methods: A total of 65 cases of ACC from minor and major salivary glands were included in this study. We evaluated tumor budding, tumor-infiltrating lymphocytes (TILs), and tumor-stroma ratio (TSR) in hematoxylin and eosin (HE) stained sections.

Results: Stroma-rich ACCs recurred more frequently (p = 0.029) during follow-up and associated with distant metastasis (p = 0.038). In multivariable analysis, stroma-rich tumors associated with poorer disease-specific survival with a hazard ratio of 3.76 (95% CI 1.10-12.83, p = 0.034). ACCs commonly showed a low infiltration of TILs as 89% of the tumors was characterized by an immune desert pattern. Low infiltration of TILs associated significantly with increased tumor budding (p = 0.039).

Conclusion: Adverse features of TSR and tumor budding are widely expressed in ACC, and stroma-rich tumors are associated with poor prognosis. Low number of TILs in ACC tissue indicates a weak immune response by the host and illustrates the nature of ACC as a relentless malignancy.

Background: Oral lichen planus (OLP) is a T cell-mediated immune disease. Iguratimod (IGU) is a novel immunomodulatory agent for rheumatoid arthritis. No studies have been reported on the mechanism of IGU in the treatment of OLP, which deserves investigation.

Methods: Samples were collected from two batches of non-erosive OLP, erosive OLP (EOLP) patients and healthy control subjects. In the first batch, the effects of IGU or the same volume of dimethyl sulfoxide (DMSO) on proliferation, apoptosis and migration of peripheral blood T lymphocytes (PBL T) were examined by CCK-8, flow cytometry and transwell assay respectively. The levels of IL-6, IL-17, TNF-α, TGF-β and IL-10 were measured by enzyme-linked immunosorbent assay. In the second batch, the percentages of Th17 and Treg cells were determined by flow cytometry in peripheral blood mononuclear cells after IGU or DMSO stimulation.

Results: Compared with the control, IGU promoted apoptosis and inhibited migration, but had no significant effect on the proliferation of PBL T in OLP. IL-6, IL-17 and TNF-α were decreased in OLP. TGF-β and IL-10 showed an upward trend in the IGU-treated EOLP. IGU decreased Th17 in OLP and reduced Th17/Treg ratio in EOLP. The percentage of Treg cells showed an upregulated trend but the difference was not statistically significant.

Conclusion: IGU may intervene in the immune response of OLP by affecting functions of PBL T, improving the balance of Th17/Treg and regulating related cytokines.

Background: Lip exposure to carcinogens lead to several disorders, such as actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC). Although several studies have described important pathways in lip carcinogenesis, the comprehension of association of target genes in this process and their association with tumor microenvironment still need to be better understood.

Methods: Tissue samples of 30 AC and 17 LLSCC cases were included for histopathological analysis, immunohistochemical expression of CD4, CD8, and PD-L1, and fluorescence in situ hybridization for AURKA, AURKB, TP53, PTEN, CCND1, and MYC. Non-parametrical tests were done and p < 0.05 was considered significant.

Results: LLSCC patients presented higher amplifications of AURKA and AURKB, deletion of TP53, and PTEN and rearrangements of MYC than AC. AURKA, AURKB, TP53, PTEN, and CCND1 changes were correlated with PD-L1 expression.

Conclusions: AURKA and AURKB amplifications and other gene changes are pointed by their association of lip disorders.

Background: The terminology surrounding developmental lesions in the oral cavity is widely applied, often leading to confusion in differentiating between developmental malformations and neoplasia. Odontogenic tumor classification includes both true neoplasms and malformations which make it very complex and dynamic.

Method and conclusion: In this brief report, we will first discuss the concepts of malformations and neoplasia and then focusing on their relevance to odontogenic tumors, which impacts their classification and treatment, particularly mixed odontogenic lesions.

Background: The inactivation of tumor suppressor genes (TSGs) caused by abnormal DNA methylation is confirmed to be widely present in oral potential malignant diseases (OPMDs). Carotenoids like lycopene and astaxanthin can regulate DNA methylation and exert anticancer effects. Therapeutic effect of astaxanthin in OPMDs and oral squamous cell carcinoma (OSCC) models is confirmed, but the relationship between the anti-cancer ability of astaxanthin and its DNA methylation regulation ability remains unclear.

Methods: Whole-genome bisulfite sequencing (WGBS) were used to provide biological information associated with DNA methylation. Methylation specific PCR was used to detect the methylation level of specific sites. Related markers were evaluated by qRT-PCR and western blot. CCK8 assay, cell scratch assay, flow cytometric analysis were performed to investigate the cell viability, migration, cell cycle, and apoptosis after treated with concentrations of astaxanthin.

Results: WGBS revealed that HOXA3 and SOX1 were the TSGs with significant differences in promoter CpG methylation of oral dysplastic keratinocytes (DOK) cells. After treatment with 8 μM astaxanthin, the promoter CpG methylation levels of the TSGs were significantly reduced, resulting in the increase in gene expression. The overall effect of astaxanthin on DOK cells is inhibiting cell viability, reducing cell migration, leading to cell cycle G₀/G₁ arrest, and promoting apoptosis.

Conclusions: This study confirmed significant differences in DNA methylation patterns among oral normal, dysplastic, and cancerous cells. Astaxanthin can reduce the promoter CpG methylation level of TSGs by reducing DNA methyltransferase 1 protein expression level, upregulating mRNA and protein expression, and subsequently modulating the biological behavior of DOK.

Background: Mucinous cells can be detected sporadically or may constitute the primary tumor component in salivary gland tumors, as observed in the intraductal papillary mucinous neoplasm (IPMN). This low-grade tumor is composed of mucinous columnar cells organized into papillary cystic structures. The present study aimed to compare the mucous cells in IPMN with mucous cells present in mucoepidermoid carcinoma (MEC) and papillary cystadenoma (PC).

Methods: Immunohistochemistry analysis was carried out to compare the mucous cells in IPMN with the sporadic mucous cells in MEC (n = 4) and PC (n = 3).

Results: The results indicated that IPMN cells were positive for CK7, CK18, DOG1, and NKX3.1 and negative for CK14, SMA, and p63. The mucous cells in both MEC and PC were positive for CK7 and negative for CK18, SMA, DOG1, and NKX3.1. The positive expression of CK14 and p63 revealed the presence of basal cells both in PC, cystic areas of MEC, and normal mucous salivary glands.

Conclusion: The immunohistochemical profile of IPMN closely resembles that of the mucous cells of the minor salivary glands yet differs from the mucous cells observed in MEC and PCX. This suggests that IPMN is probably derived from the transformation of secretory cells of the minor mucous salivary gland and has no rimming/basal cells. For this reason, we propose that this tumor is designated as mucous acinic cell carcinoma.

Background: Oropharyngeal squamous cell carcinoma (OP-SCC) represents a public health problem and human papillomavirus (HPV) is one of the risk factors. Neutrophil extracellular traps (NET) are meshes of DNA strands and granule proteins. NET has been identified in diverse cancers, whether associated with viruses or not. However, there is no information on NET in OP-SCC. We aimed to evaluate the NET release by neutrophils in the OP-SCC microenvironment, stratified by HPV status.

Methods: This cross-sectional study analyzed OP-SCC biopsy specimens diagnosed from 1997 to 2021. HPV status was determined by p16 immunohistochemistry and "in situ" hybridization. Neutrophils were detected by CD66b immunohistochemistry. Immunofluorescence was used to identify NET by co-localization of myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit). Bivariate statistics, Kaplan-Meier survival analysis, and the log-rank test were performed.

Results: HPV-positive and HPV-negative OP-SCC had similar CD66b + neutrophil infiltration (p > 0.05), but the release of NET was significantly increased in HPV-positive compared to HPV-negative OP-SCC samples (p < 0.05). Overall survival was not impacted by NET indexes (p > 0.05).

Conclusion: The presence of HPV may stimulate NET release in the OP-SCC microenvironment.