Pathology, research and practice最新文献

Cell lineage-specific immunohistochemical markers in biliary intraepithelial neoplasia: Implications for subclassification and grading

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-04 DOI: 10.1016/j.prp.2025.155896

Heiwa Tanabe , Takeshi Uehara , Hiroyoshi Ota

Biliary intraepithelial neoplasia (BilIN), a precursor to cholangiocarcinoma, is categorized into low- and high-grade based on histological characteristics. Although gastric, intestinal, and biliary phenotypes of BilIN have been identified, detailed analyses of their immunophenotypic profiles using cell lineage-specific markers remain limited. This study aimed to define the immunohistochemical profiles of BilIN lesions, subclassify them based on their immunophenotypes, and correlate these profiles with histological grades. We examined 77 BilIN lesions from extrahepatic bile ducts, including 30 low- and 47 high-grade lesions, using immunohistochemical staining for gastric (claudin-18, MUC5AC), intestinal (cadherin-17, glycoprotein A33), and biliary (carbohydrate sulfotransferase 4) markers, along with progression markers (S100P, IMP3). Expression levels were semiquantitatively scored and correlated with histopathological features. BilIN lesions were classified into four immunophenotypes: gastric (G-type), intestinal (I-type), gastrointestinal (GI-type), and biliary (B-type). Low-grade lesions comprised G- (33.3 %), GI- (40 %), I- (13.3 %), and B-types (13.3 %), while high-grade lesions included G- (40.4 %), GI- (29.8 %), I- (21.3 %), and B-types (8.5 %). In low-grade BilIN, G-type lesions corresponded to gastric mucous cells, I-type to intestinal epithelial cells, and B-type to bile duct epithelial cells, while most GI-type lesions exhibited mixed G- and I-type components. High-grade BilIN differentiation based solely on histological characteristics was challenging to delineate due to overlapping features among I-, GI-, and B-type cells. S100P and IMP3 expression levels were significantly elevated in high-grade lesions, particularly within the I+B-type BilIN group, with no notable differences in G- or GI-type BilIN. Immunophenotypic profiling with lineage-specific markers effectively subclassified BilIN, enhancing the understanding of its histogenesis and progression.

{"title":"Cell lineage-specific immunohistochemical markers in biliary intraepithelial neoplasia: Implications for subclassification and grading","authors":"Heiwa Tanabe , Takeshi Uehara , Hiroyoshi Ota","doi":"10.1016/j.prp.2025.155896","DOIUrl":"10.1016/j.prp.2025.155896","url":null,"abstract":"<div><div>Biliary intraepithelial neoplasia (BilIN), a precursor to cholangiocarcinoma, is categorized into low- and high-grade based on histological characteristics. Although gastric, intestinal, and biliary phenotypes of BilIN have been identified, detailed analyses of their immunophenotypic profiles using cell lineage-specific markers remain limited. This study aimed to define the immunohistochemical profiles of BilIN lesions, subclassify them based on their immunophenotypes, and correlate these profiles with histological grades. We examined 77 BilIN lesions from extrahepatic bile ducts, including 30 low- and 47 high-grade lesions, using immunohistochemical staining for gastric (claudin-18, MUC5AC), intestinal (cadherin-17, glycoprotein A33), and biliary (carbohydrate sulfotransferase 4) markers, along with progression markers (S100P, IMP3). Expression levels were semiquantitatively scored and correlated with histopathological features. BilIN lesions were classified into four immunophenotypes: gastric (G-type), intestinal (I-type), gastrointestinal (GI-type), and biliary (B-type). Low-grade lesions comprised G- (33.3 %), GI- (40 %), I- (13.3 %), and B-types (13.3 %), while high-grade lesions included G- (40.4 %), GI- (29.8 %), I- (21.3 %), and B-types (8.5 %). In low-grade BilIN, G-type lesions corresponded to gastric mucous cells, I-type to intestinal epithelial cells, and B-type to bile duct epithelial cells, while most GI-type lesions exhibited mixed G- and I-type components. High-grade BilIN differentiation based solely on histological characteristics was challenging to delineate due to overlapping features among I-, GI-, and B-type cells. S100P and IMP3 expression levels were significantly elevated in high-grade lesions, particularly within the I+B-type BilIN group, with no notable differences in G- or GI-type BilIN. Immunophenotypic profiling with lineage-specific markers effectively subclassified BilIN, enhancing the understanding of its histogenesis and progression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155896"},"PeriodicalIF":2.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracytoplasmic accumulation of keratan sulfate is a hallmark of granular cell tumor

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-03 DOI: 10.1016/j.prp.2025.155892

Hitomi Hoshino , Akifumi Muramoto , Tomoya O. Akama , Hisato Yoshida , Natsumi Yonemoto , Mana Fukushima , Motohiro Kobayashi

Granular cell tumor (GCT) is a relatively rare neoplasm characterized by abundant eosinophilic intracytoplasmic granules. More than three decades ago, Ehara and Katsuyama reported that GCT granules are recognized by the anti-keratan sulfate (KS) monoclonal antibody 5D4 and suggested that 5D4 could serve as a diagnostic marker for GCT. However, due to the small number of samples analyzed and incomplete structural analysis of KS, use of 5D4 as a GCT marker has not yet been widely accepted. To confirm its use as a GCT marker, we performed quantitative immunohistochemical analysis of GCT (n = 27) and other GCT-mimicking tumors/lesions (n = 82) including schwannoma (n = 10), neurofibroma (n = 10), melanocytic nevus (n = 10), leiomyoma (n = 10), gastrointestinal stromal tumor (GIST) (n = 10), malignant melanoma (n = 10), dermatofibroma (n = 10), angiosarcoma (n = 10) and malakoplakia (n = 2) using 5D4 and two other anti-KS monoclonal antibodies, R-10G and 297–11A, in combination with two endoglycosidases, keratanase II and endo-β-galactosidase. We found that most GCT tissues were immunostained with 5D4 and 297–11A, although tumors/lesions mimicking GCT showed minimal staining. Moreover, structural analysis revealed that KS accumulated in GCT consisted of both highly sulfated and low-sulfated KS located at non-reducing and reducing termini, respectively. Here we propose that intracytoplasmic KS accumulation is a hallmark of GCT, and that 5D4 and 297–11A could serve as diagnostic markers of GCT.

{"title":"Intracytoplasmic accumulation of keratan sulfate is a hallmark of granular cell tumor","authors":"Hitomi Hoshino , Akifumi Muramoto , Tomoya O. Akama , Hisato Yoshida , Natsumi Yonemoto , Mana Fukushima , Motohiro Kobayashi","doi":"10.1016/j.prp.2025.155892","DOIUrl":"10.1016/j.prp.2025.155892","url":null,"abstract":"<div><div>Granular cell tumor (GCT) is a relatively rare neoplasm characterized by abundant eosinophilic intracytoplasmic granules. More than three decades ago, Ehara and Katsuyama reported that GCT granules are recognized by the anti-keratan sulfate (KS) monoclonal antibody 5D4 and suggested that 5D4 could serve as a diagnostic marker for GCT. However, due to the small number of samples analyzed and incomplete structural analysis of KS, use of 5D4 as a GCT marker has not yet been widely accepted. To confirm its use as a GCT marker, we performed quantitative immunohistochemical analysis of GCT (<em>n</em> = 27) and other GCT-mimicking tumors/lesions (<em>n</em> = 82) including schwannoma (<em>n</em> = 10), neurofibroma (<em>n</em> = 10), melanocytic nevus (<em>n</em> = 10), leiomyoma (<em>n</em> = 10), gastrointestinal stromal tumor (GIST) (<em>n</em> = 10), malignant melanoma (<em>n</em> = 10), dermatofibroma (<em>n</em> = 10), angiosarcoma (<em>n</em> = 10) and malakoplakia (<em>n</em> = 2) using 5D4 and two other anti-KS monoclonal antibodies, R-10G and 297–11A, in combination with two endoglycosidases, keratanase II and endo-β-galactosidase. We found that most GCT tissues were immunostained with 5D4 and 297–11A, although tumors/lesions mimicking GCT showed minimal staining. Moreover, structural analysis revealed that KS accumulated in GCT consisted of both highly sulfated and low-sulfated KS located at non-reducing and reducing termini, respectively. Here we propose that intracytoplasmic KS accumulation is a hallmark of GCT, and that 5D4 and 297–11A could serve as diagnostic markers of GCT.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155892"},"PeriodicalIF":2.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The m6A reader YTHDC2 restrains endometrial cancer progression through suppressing hedgehog signaling pathway

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-28 DOI: 10.1016/j.prp.2025.155879

Xinyan Zhang , Man Gao , Hongyun Ma , Zhao Ma , Tengqi Wang , Wen Gao , Qin Si , Ning Li , Yongping Mu , Fei Liu

N6-methyladenosine (m⁶A) is a prevalent RNA modification involved in different physiological and pathological processes. However, little is known about the role of m⁶A modification in endometrial cancer (EC). In this study, we explored the expression and prognosis of m⁶A-related genes in EC using public databases to screen relevantgenes. Quantitative reverse-transcription PCR and immunohistochemistry were performed to detect YTH N6-methyladenosine RNA binding protein C2 (YTHDC2) expression in EC tissues, and the relationships between YTHDC2 expression, pathological features, and prognosis were analyzed. The effect of YTHDC2 on EC cells and its mechanism of action were examined in vitro and in vivo. YTHDC2 was identified as a tumor suppressor gene in EC. Expression of YTHDC2 mRNA and protein was significantly lower in EC tissues than in normal tissues. YTHDC2 expression was related to myometrial invasion (χ²=7.523, P = 0.006), lymph node metastasis (χ²=7.203, P = 0.007), and FIGO stage (χ²=9.678, P = 0.008) in EC. It was also a prognostic factor in EC (95 %CI: 1.217–3.646, P = 0.013), and patients with EC low YTHDC2 expression had poor overall survival. YTHDC2 knockdown promoted the proliferation, migration, and invasion of EC cells, and decreased apoptosis. Upregulation of YTHDC2 showed the opposite effects. YTHDC2 inhibited the Hedgehog signaling pathway, and the Hedgehog inhibitor vismodegib partly eliminated the effects of YTHDC2 knockdown of EC cells. YTHDC2 inhibited EC progression and has the potential to be explored as an independent prognostic factor in patients with EC.

{"title":"The m6A reader YTHDC2 restrains endometrial cancer progression through suppressing hedgehog signaling pathway","authors":"Xinyan Zhang , Man Gao , Hongyun Ma , Zhao Ma , Tengqi Wang , Wen Gao , Qin Si , Ning Li , Yongping Mu , Fei Liu","doi":"10.1016/j.prp.2025.155879","DOIUrl":"10.1016/j.prp.2025.155879","url":null,"abstract":"<div><div>N6-methyladenosine (m<sup>6</sup>A) is a prevalent RNA modification involved in different physiological and pathological processes. However, little is known about the role of m<sup>6</sup>A modification in endometrial cancer (EC). In this study, we explored the expression and prognosis of m<sup>6</sup>A-related genes in EC using public databases to screen relevantgenes. Quantitative reverse-transcription PCR and immunohistochemistry were performed to detect YTH N6-methyladenosine RNA binding protein C2 (YTHDC2) expression in EC tissues, and the relationships between YTHDC2 expression, pathological features, and prognosis were analyzed. The effect of YTHDC2 on EC cells and its mechanism of action were examined in vitro and in vivo. YTHDC2 was identified as a tumor suppressor gene in EC. Expression of YTHDC2 mRNA and protein was significantly lower in EC tissues than in normal tissues. YTHDC2 expression was related to myometrial invasion (χ<sup>2</sup>=7.523, <em>P</em> = 0.006), lymph node metastasis (χ<sup>2</sup>=7.203, <em>P</em> = 0.007), and FIGO stage (χ<sup>2</sup>=9.678, <em>P</em> = 0.008) in EC. It was also a prognostic factor in EC (95 %CI: 1.217–3.646, <em>P</em> = 0.013), and patients with EC low YTHDC2 expression had poor overall survival. YTHDC2 knockdown promoted the proliferation, migration, and invasion of EC cells, and decreased apoptosis. Upregulation of YTHDC2 showed the opposite effects. YTHDC2 inhibited the Hedgehog signaling pathway, and the Hedgehog inhibitor vismodegib partly eliminated the effects of YTHDC2 knockdown of EC cells. YTHDC2 inhibited EC progression and has the potential to be explored as an independent prognostic factor in patients with EC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155879"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationship of lymphatic vessel invasion and density with clinicopathological parameters and survival in patients with gastric carcinoma: A systematic review and meta-analysis

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-28 DOI: 10.1016/j.prp.2025.155877

Dimitrios N. Varvarousis , Aikaterini A. Marini , Georgios Ntritsos , Alexandra Barbouti , Panagiotis V. Kitsoulis , Panagiotis E. Kanavaros

The purpose of this study was to conduct a comprehensive review and meta-analysis to investigate the possible relationship of lymphatic vessel invasion (LVI) and lymphatic vessel density (LVD), evaluated using immunohistochemistry, with survival and clinicopathological parameters in patients with gastric carcinoma. The principal result of this meta-analysis was the statistically significant correlation between LVI and presence of lymph node metastasis. This finding, in view of previous data showing that lymph node metastasis is associated with decreased survival, suggests that LVI may be a negative prognostic factor in gastric carcinoma. In contrast, LVD, whether assessed overall, intratumorally, or peritumorally, showed no statistically significant correlation with survival. The major conclusion of this meta-analysis is that LVI is an important indicator of aggressiveness of gastric carcinomas and may be a negative prognostic factor because of the strong association between LVI and presence of lymph node metastasis.

{"title":"Relationship of lymphatic vessel invasion and density with clinicopathological parameters and survival in patients with gastric carcinoma: A systematic review and meta-analysis","authors":"Dimitrios N. Varvarousis , Aikaterini A. Marini , Georgios Ntritsos , Alexandra Barbouti , Panagiotis V. Kitsoulis , Panagiotis E. Kanavaros","doi":"10.1016/j.prp.2025.155877","DOIUrl":"10.1016/j.prp.2025.155877","url":null,"abstract":"<div><div>The purpose of this study was to conduct a comprehensive review and meta-analysis to investigate the possible relationship of lymphatic vessel invasion (LVI) and lymphatic vessel density (LVD), evaluated using immunohistochemistry, with survival and clinicopathological parameters in patients with gastric carcinoma. The principal result of this meta-analysis was the statistically significant correlation between LVI and presence of lymph node metastasis. This finding, in view of previous data showing that lymph node metastasis is associated with decreased survival, suggests that LVI may be a negative prognostic factor in gastric carcinoma. In contrast, LVD, whether assessed overall, intratumorally, or peritumorally, showed no statistically significant correlation with survival. The major conclusion of this meta-analysis is that LVI is an important indicator of aggressiveness of gastric carcinomas and may be a negative prognostic factor because of the strong association between LVI and presence of lymph node metastasis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155877"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking the secrets of single extracellular vesicles by cutting-edge technologies 用尖端技术揭开单个细胞外囊泡的秘密

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-28 DOI: 10.1016/j.prp.2025.155878

Ramya Lakshmi Rajendran , Prakash Gangadaran , Subhrojyoti Ghosh , ArulJothi Kandasamy Nagarajan , Rijula Batabyal , Byeong-Cheol Ahn

Extracellular vesicles (EVs), isolated through techniques such as liquid biopsy, have emerged as crucial biomarkers in various diseases, including cancer. EVs were dismissed initially as cellular debris, EVs are now recognized for their role in intercellular communication, carrying proteins, RNAs, and other molecules between cells. Their stability in biofluids and ability to mirror their parent cells' molecular composition make them attractive candidates for non-invasive diagnostics. EVs, including microvesicles and exosomes, contribute to immune modulation and cancer progression, presenting both therapeutic challenges and opportunities. However, despite advances in analytical techniques like high-resolution microscopy and nanoparticle tracking analysis (NTA), standardization in EV isolation and characterization remains a hurdle. Cutting-edge technologies, such as atomic force microscopy and Raman tweezers microspectroscopy, have enhanced our understanding of single EVs, yet issues like low throughput and high technical complexity limit their widespread application. Other technologies like transmission electron microscopy, cryogenic transmission electron microscopy, super-resolution microscopy, direct stochastic optical reconstruction microscopy, single-molecule localization microscopy, tunable resistive pulse sensing, single-particle interferometric reflectance imaging sensor, flow cytometry, droplet digital analysis, total internal reflection fluorescence also contribute to EV analysis. Future research must focus on improving detection methods, developing novel analytical platforms, and integrating artificial intelligence to enhance the specificity of EV characterization. The future of EV research holds promise for breakthroughs in precision medicine, with a collaborative effort needed to translate these advancements into clinical practice.

{"title":"Unlocking the secrets of single extracellular vesicles by cutting-edge technologies","authors":"Ramya Lakshmi Rajendran , Prakash Gangadaran , Subhrojyoti Ghosh , ArulJothi Kandasamy Nagarajan , Rijula Batabyal , Byeong-Cheol Ahn","doi":"10.1016/j.prp.2025.155878","DOIUrl":"10.1016/j.prp.2025.155878","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), isolated through techniques such as liquid biopsy, have emerged as crucial biomarkers in various diseases, including cancer. EVs were dismissed initially as cellular debris, EVs are now recognized for their role in intercellular communication, carrying proteins, RNAs, and other molecules between cells. Their stability in biofluids and ability to mirror their parent cells' molecular composition make them attractive candidates for non-invasive diagnostics. EVs, including microvesicles and exosomes, contribute to immune modulation and cancer progression, presenting both therapeutic challenges and opportunities. However, despite advances in analytical techniques like high-resolution microscopy and nanoparticle tracking analysis (NTA), standardization in EV isolation and characterization remains a hurdle. Cutting-edge technologies, such as atomic force microscopy and Raman tweezers microspectroscopy, have enhanced our understanding of single EVs, yet issues like low throughput and high technical complexity limit their widespread application. Other technologies like transmission electron microscopy, cryogenic transmission electron microscopy, super-resolution microscopy, direct stochastic optical reconstruction microscopy, single-molecule localization microscopy, tunable resistive pulse sensing, single-particle interferometric reflectance imaging sensor, flow cytometry, droplet digital analysis, total internal reflection fluorescence also contribute to EV analysis. Future research must focus on improving detection methods, developing novel analytical platforms, and integrating artificial intelligence to enhance the specificity of EV characterization. The future of EV research holds promise for breakthroughs in precision medicine, with a collaborative effort needed to translate these advancements into clinical practice.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155878"},"PeriodicalIF":2.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

E2F transcription factor 1 as a potential prognostic biomarker and promotes tumor proliferation in skin cutaneous melanoma

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-27 DOI: 10.1016/j.prp.2025.155875

Ying Liu , Dan Luo , Yuangang Lu , Liuchang Tan

Cutaneous melanoma (SKCM) is a highly aggressive malignancy with an overall poor prognosis. The expression of E2F transcription factor 1 in SKCM tissues was analyzed using the data acquired from the Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO)databases. The expression of E2F1 was also analyzed in human biopsies using immunohistology, and its expression was detected in SKCM cell lines using qPCR and WB technology. The prognostic value of E2F transcription factor 1 in SKCM was investigated using Kaplan-Meier survival and Cox analysis. The Tumor Immunization Estimation Resource (TIMER) was used to analyze the invasion of immune cells and associated markers of immune cells. The prognostic value of E2F transcription factor 1 DNA methylation levels for each CpG was analyzed by means of the MethSurv. The results were verified in the Human Protein Atlas (HPA) database. Individuals with elevated E2F transcription factor 1 expression had a worse prognosis (HR=1.43, p = 0.01). Using the expression level of E2F transcription factor 1, a reliable distinction between tumor and normal tissues can be made (Area Under the Curve =0.949). Moreover, immune infiltrations analysis showed that the mRNA expression levels and somatic copy number alterations (SCNA) in E2F transcription factor 1 were significantly correlated with recruitment of several immune cells. Our study showed that overexpression of E2F transcription factor 1 was significantly associated with poor prognosis and malignant phenotype of melanoma cells in SKCM patients.

{"title":"E2F transcription factor 1 as a potential prognostic biomarker and promotes tumor proliferation in skin cutaneous melanoma","authors":"Ying Liu , Dan Luo , Yuangang Lu , Liuchang Tan","doi":"10.1016/j.prp.2025.155875","DOIUrl":"10.1016/j.prp.2025.155875","url":null,"abstract":"<div><div>Cutaneous melanoma (SKCM) is a highly aggressive malignancy with an overall poor prognosis. The expression of E2F transcription factor 1 in SKCM tissues was analyzed using the data acquired from the Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO)databases. The expression of E2F1 was also analyzed in human biopsies using immunohistology, and its expression was detected in SKCM cell lines using qPCR and WB technology. The prognostic value of E2F transcription factor 1 in SKCM was investigated using Kaplan-Meier survival and Cox analysis. The Tumor Immunization Estimation Resource (TIMER) was used to analyze the invasion of immune cells and associated markers of immune cells. The prognostic value of E2F transcription factor 1 DNA methylation levels for each CpG was analyzed by means of the MethSurv. The results were verified in the Human Protein Atlas (HPA) database. Individuals with elevated E2F transcription factor 1 expression had a worse prognosis (HR=1.43, p = 0.01). Using the expression level of E2F transcription factor 1, a reliable distinction between tumor and normal tissues can be made (Area Under the Curve =0.949). Moreover, immune infiltrations analysis showed that the mRNA expression levels and somatic copy number alterations (SCNA) in E2F transcription factor 1 were significantly correlated with recruitment of several immune cells. Our study showed that overexpression of E2F transcription factor 1 was significantly associated with poor prognosis and malignant phenotype of melanoma cells in SKCM patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155875"},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tiny messengers, big Impact: Exosomes driving EMT in oral cancer

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-27 DOI: 10.1016/j.prp.2025.155873

Hassan Mivehchi , Aisan Eskandari-Yaghbastlo , Sahand Emrahoglu , Sahand Saeidpour Masouleh , Farbod Faghihinia , Saminalsadat Ayoubi , Mohsen Nabi Afjadi

Exosomes are indispensable extracellular vesicles that facilitate intercellular communication and are crucial for both healthy and pathological conditions, including cancer. The capacity of exosomes to echo the molecular characteristics of their cells of origin, including malignant cells, makes them indispensable tools for diagnosing and tracking disease progression in the field of oncology. Oral squamous cell carcinoma (OSCC), which has been identified as the sixth most prevalent cancer worldwide, has been linked to numerous risk factors, including tobacco use, alcohol consumption, human papillomavirus (HPV) infection, and inadequate oral hygiene. Exosomes pointedly influence the advancement of oral cancer via promoting tumor cell growth, invasion, angiogenesis, and immune evasion through the alteration of the tumor microenvironment. A critical apparatus in cancer metastasis is the epithelial-to-mesenchymal transition (EMT), during which cancer cells acquire improved migratory and invasive properties. EMT plays a role in metastasis, resistance to treatment, and evasion of the immune response. Exosomes facilitate EMT in oral cancer by delivering bioactive molecules that influence EMT signaling pathways. These exosomes inspire EMT in recipient cells, by this means enhancing tumor invasion and metastasis. This study aims to identify the specific exosomal components and signaling pathways that are tangled in EMT, in that way providing new avenues for targeted therapies designed to hinder the metastasis of oral cancer.

{"title":"Tiny messengers, big Impact: Exosomes driving EMT in oral cancer","authors":"Hassan Mivehchi , Aisan Eskandari-Yaghbastlo , Sahand Emrahoglu , Sahand Saeidpour Masouleh , Farbod Faghihinia , Saminalsadat Ayoubi , Mohsen Nabi Afjadi","doi":"10.1016/j.prp.2025.155873","DOIUrl":"10.1016/j.prp.2025.155873","url":null,"abstract":"<div><div>Exosomes are indispensable extracellular vesicles that facilitate intercellular communication and are crucial for both healthy and pathological conditions, including cancer. The capacity of exosomes to echo the molecular characteristics of their cells of origin, including malignant cells, makes them indispensable tools for diagnosing and tracking disease progression in the field of oncology. Oral squamous cell carcinoma (OSCC), which has been identified as the sixth most prevalent cancer worldwide, has been linked to numerous risk factors, including tobacco use, alcohol consumption, human papillomavirus (HPV) infection, and inadequate oral hygiene. Exosomes pointedly influence the advancement of oral cancer via promoting tumor cell growth, invasion, angiogenesis, and immune evasion through the alteration of the tumor microenvironment. A critical apparatus in cancer metastasis is the epithelial-to-mesenchymal transition (EMT), during which cancer cells acquire improved migratory and invasive properties. EMT plays a role in metastasis, resistance to treatment, and evasion of the immune response. Exosomes facilitate EMT in oral cancer by delivering bioactive molecules that influence EMT signaling pathways. These exosomes inspire EMT in recipient cells, by this means enhancing tumor invasion and metastasis. This study aims to identify the specific exosomal components and signaling pathways that are tangled in EMT, in that way providing new avenues for targeted therapies designed to hinder the metastasis of oral cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"268 ","pages":"Article 155873"},"PeriodicalIF":2.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular mechanisms of lncRNA NEAT1 in the pathogenesis of liver-related diseases, with special focus on therapeutic approaches

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-26 DOI: 10.1016/j.prp.2025.155867

Yahui Wang , Gaurav Sanghvi , Suhas Ballal , RSK Sharma , Piyus Kumar Pathak , Aman Shankhyan , Jiaxuan Sun , Qingmin Chen , Yu Ma , Lei Huang , Yahui Liu

Liver diseases are a major worldwide health concern, with high rates of dysfunction and mortality. In recent years, a variety of lncRNAs have been studied and discovered to be engaged in numerous cellular-level regulatory mechanisms as competing endogenous RNAs (ceRNAs), which play a significant role in the development of liver-related diseases. A class of RNA molecules known as lncRNAs, which are over 200 nucleotides long, do not translate into proteins. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a type of lncRNA that has a critical function in paraspeckles formation and stability. NEAT1 levels are consistently found to be higher than normal in a number of different types of diseases, as well as patients who have high levels of NEAT1 expression often have a poor prognosis. The significance and mode of action of NEAT1 in liver illnesses, such as nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), liver fibrosis/cirrhosis, hepatocellular carcinoma (HCC), viral hepatitis, and liver injury, are becoming more widely known. In this review, we highlighted significant recent studies concerning the various roles of lncRNA NEAT1 in hepatic diseases. As well as, we reviewed novel therapeutic potential of lncRNAs in several liver-related diseases.

{"title":"Molecular mechanisms of lncRNA NEAT1 in the pathogenesis of liver-related diseases, with special focus on therapeutic approaches","authors":"Yahui Wang , Gaurav Sanghvi , Suhas Ballal , RSK Sharma , Piyus Kumar Pathak , Aman Shankhyan , Jiaxuan Sun , Qingmin Chen , Yu Ma , Lei Huang , Yahui Liu","doi":"10.1016/j.prp.2025.155867","DOIUrl":"10.1016/j.prp.2025.155867","url":null,"abstract":"<div><div>Liver diseases are a major worldwide health concern, with high rates of dysfunction and mortality. In recent years, a variety of lncRNAs have been studied and discovered to be engaged in numerous cellular-level regulatory mechanisms as competing endogenous RNAs (ceRNAs), which play a significant role in the development of liver-related diseases. A class of RNA molecules known as lncRNAs, which are over 200 nucleotides long, do not translate into proteins. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a type of lncRNA that has a critical function in paraspeckles formation and stability. NEAT1 levels are consistently found to be higher than normal in a number of different types of diseases, as well as patients who have high levels of NEAT1 expression often have a poor prognosis. The significance and mode of action of NEAT1 in liver illnesses, such as nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), liver fibrosis/cirrhosis, hepatocellular carcinoma (HCC), viral hepatitis, and liver injury, are becoming more widely known. In this review, we highlighted significant recent studies concerning the various roles of lncRNA NEAT1 in hepatic diseases. As well as, we reviewed novel therapeutic potential of lncRNAs in several liver-related diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155867"},"PeriodicalIF":2.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic and molecular profiling in Merkel Cell Carcinoma: Focus on MCPyV oncoproteins and emerging diagnostic techniques.

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-26 DOI: 10.1016/j.prp.2025.155869

Harpreet Singh, Sourav Mohanto, Anil Kumar, Arun Kumar Mishra, Arvind Kumar, Amrita Mishra, Mohammed Gulzar Ahmed, Mukesh Kr Singh, Amrendra Pratap Yadav, Shivani Chopra, Hitesh Chopra

Merkel Cell Carcinoma (MCC) is an uncommon yet highly malignant form of skin cancer, frequently linked to the Merkel cell polyomavirus (MCPyV). This review comprehensively covers data from year 2000 to 2024, employing keywords such as MCC, MCPyV Oncoproteins, Immunohistochemistry, Southern Blot, Western Blot, Polymerase Chain Reaction (PCR), Digital Droplet PCR (ddPCR), Next-Generation Sequencing (NGS), and In Situ Hybridization (ISH). The search engines utilized were Google, PubMed Central, Scopus, and other journal databases like ScienceDirect. This review is essential for researchers and the broader medical community as it consolidates two decades of research on the genetic and molecular profiling of MCC, particularly focusing on MCPyV's role in its pathogenesis. It highlights the diagnostic advancements and therapeutic potential of targeting viral oncoproteins and provides insights into the development of both in vivo and in vitro models for better understanding MCC. The findings emphasize the significance of early detection, molecular diagnostics, and personalized treatment approaches, aiming to improve outcomes for patients with this malignant malignancy.

{"title":"Genetic and molecular profiling in Merkel Cell Carcinoma: Focus on MCPyV oncoproteins and emerging diagnostic techniques.","authors":"Harpreet Singh, Sourav Mohanto, Anil Kumar, Arun Kumar Mishra, Arvind Kumar, Amrita Mishra, Mohammed Gulzar Ahmed, Mukesh Kr Singh, Amrendra Pratap Yadav, Shivani Chopra, Hitesh Chopra","doi":"10.1016/j.prp.2025.155869","DOIUrl":"https://doi.org/10.1016/j.prp.2025.155869","url":null,"abstract":"<p><p>Merkel Cell Carcinoma (MCC) is an uncommon yet highly malignant form of skin cancer, frequently linked to the Merkel cell polyomavirus (MCPyV). This review comprehensively covers data from year 2000 to 2024, employing keywords such as MCC, MCPyV Oncoproteins, Immunohistochemistry, Southern Blot, Western Blot, Polymerase Chain Reaction (PCR), Digital Droplet PCR (ddPCR), Next-Generation Sequencing (NGS), and In Situ Hybridization (ISH). The search engines utilized were Google, PubMed Central, Scopus, and other journal databases like ScienceDirect. This review is essential for researchers and the broader medical community as it consolidates two decades of research on the genetic and molecular profiling of MCC, particularly focusing on MCPyV's role in its pathogenesis. It highlights the diagnostic advancements and therapeutic potential of targeting viral oncoproteins and provides insights into the development of both in vivo and in vitro models for better understanding MCC. The findings emphasize the significance of early detection, molecular diagnostics, and personalized treatment approaches, aiming to improve outcomes for patients with this malignant malignancy.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":" ","pages":"155869"},"PeriodicalIF":2.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

METTL3 enhances esophageal squamous cell carcinoma progression by suppressing ferroptosis through the PBX3/CA9 cascade

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-02-26 DOI: 10.1016/j.prp.2025.155865

Lingxia Yang , Chang'e Ding , Mengjie Tuo , Tiandong Chu , Ping Liu

Background

N⁶-methyladenosine (m⁶A) modification controls various processes during tumorigenesis. Although METTL3 functions as a pro-tumorigenic driver in esophageal squamous cell carcinoma (ESCC), its mechanisms are largely unknown.

Methods

mRNA expression was detected by quantitative PCR, and protein expression was assessed by immunoblotting. Cell motility, invasiveness, and apoptosis were analyzed by wound-healing assay, transwell assay and flow cytometry, respectively. Cell ferroptosis was assessed by detecting the contents of ROS, MDA and Fe²⁺. The METTL3/PBX3 and PBX3/CA9 relationships were validated by luciferase, MeRIP or ChIP assay. The effect of METTL3 on tumor growth was tested by xenograft studies.

Results

METTL3 was enhanced in ESCC tumors and cells, and its deficiency suppressed ESCC cell migration and invasion and promoted cell apoptosis and ferroptosis. Additionally, METTL3 deficiency caused growth inhibition of ESCC xenografts in vivo. METTL3 enhanced m6A modification of PBX3 mRNA. PBX3 was identified as a mediator of METTL3 function in modulating ESCC cell phenotypes. PBX3 promoted CA9 transcription, and METTL3 positively regulated CA9 through PBX3. PBX3 deficiency impeded ESCC cell migration and invasion and enhanced cell apoptosis and ferroptosis by downregulating CA9.

Conclusion

Our study elucidates a novel mechanism, the METTL3/PBX3/CA9 cascade, underlying the oncogenic activity of METTL3 in ESCC. The novel cascade may represent the potential target for ESCC therapy in the future.

{"title":"METTL3 enhances esophageal squamous cell carcinoma progression by suppressing ferroptosis through the PBX3/CA9 cascade","authors":"Lingxia Yang , Chang'e Ding , Mengjie Tuo , Tiandong Chu , Ping Liu","doi":"10.1016/j.prp.2025.155865","DOIUrl":"10.1016/j.prp.2025.155865","url":null,"abstract":"<div><h3>Background</h3><div>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification controls various processes during tumorigenesis. Although METTL3 functions as a pro-tumorigenic driver in esophageal squamous cell carcinoma (ESCC), its mechanisms are largely unknown.</div></div><div><h3>Methods</h3><div>mRNA expression was detected by quantitative PCR, and protein expression was assessed by immunoblotting. Cell motility, invasiveness, and apoptosis were analyzed by wound-healing assay, transwell assay and flow cytometry, respectively. Cell ferroptosis was assessed by detecting the contents of ROS, MDA and Fe<sup>2+</sup>. The METTL3/PBX3 and PBX3/CA9 relationships were validated by luciferase, MeRIP or ChIP assay. The effect of METTL3 on tumor growth was tested by xenograft studies.</div></div><div><h3>Results</h3><div>METTL3 was enhanced in ESCC tumors and cells, and its deficiency suppressed ESCC cell migration and invasion and promoted cell apoptosis and ferroptosis. Additionally, METTL3 deficiency caused growth inhibition of ESCC xenografts <em>in vivo</em>. METTL3 enhanced m6A modification of PBX3 mRNA. PBX3 was identified as a mediator of METTL3 function in modulating ESCC cell phenotypes. PBX3 promoted CA9 transcription, and METTL3 positively regulated CA9 through PBX3. PBX3 deficiency impeded ESCC cell migration and invasion and enhanced cell apoptosis and ferroptosis by downregulating CA9.</div></div><div><h3>Conclusion</h3><div>Our study elucidates a novel mechanism, the METTL3/PBX3/CA9 cascade, underlying the oncogenic activity of METTL3 in ESCC. The novel cascade may represent the potential target for ESCC therapy in the future.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155865"},"PeriodicalIF":2.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0