{"title":"A Proof-of-Concept Study of Digital Spatial Distance Analysis in Ovarian Mature and Immature Teratomas.","authors":"Keisuke Kanetaka, Kei Koyama, Tomonori Tsuruhashi, Hikaru Tsukita, Takahiro Ishinari, Ayana Takahashi, Ken Miyabe, Makoto Yoshida, Yukitsugu Kudo-Asabe, Hiroshi Nanjo, Kenichi Makino, Tae Sugawara, Takeo Hirakawa, Enami Kaneko, Masato Waga, Yukihiro Terada, Akiteru Goto","doi":"10.1159/pat/aehag001","DOIUrl":"10.1159/pat/aehag001","url":null,"abstract":"<p><strong>Introduction: </strong>Mature (MT) and immature teratomas (ITs) contain diverse histological components; however, their tissue-level spatial organization remains poorly understood. This proof-of-concept study aimed to develop a reproducible digital pathology workflow for quantifying the spatial distances among histological components of ovarian teratomas.</p><p><strong>Methods: </strong>Four representative mature teratoma sections and three ITs with neural elements were analyzed. Whole-slide images of hematoxylin and eosin-stained sections were manually annotated, and each morphologically recognizable component was represented by a centroid using a Python-based image analysis method. Pairwise centroid-based distances were calculated using brute-force and nearest-distance approaches, followed by an exploratory statistical analysis.</p><p><strong>Results: </strong>Anatomically related tissue pairs, including bronchial epithelium-bronchial gland and epidermis-hair follicle, showed relatively short centroid-based distances, suggesting that the workflow can capture the expected tissue-level architectural relationships. Additional associations, such as bronchial gland-bone proximity, were also observed but should be interpreted as hypothesis-generating findings. No consistent spatial proximity was observed between the immature and mature components.</p><p><strong>Conclusion: </strong>These findings support the technical feasibility of the proposed workflow for the exploratory tissue-level spatial analysis of teratomas, while emphasizing that spatial associations do not directly demonstrate biological interactions, developmental induction, or lineage relationships.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649254","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}
PathobiologyPub Date : 2026-07-30DOI: 10.1159/pat/aehag002
Iiris Maria Harjunpää, Eliisa Eveliina Viljanen, David Kalfert, Ivana Kholová
{"title":"Squamous Cells in the Thyroid Gland's Cytopathology and Histopathology: Institutional Experience.","authors":"Iiris Maria Harjunpää, Eliisa Eveliina Viljanen, David Kalfert, Ivana Kholová","doi":"10.1159/pat/aehag002","DOIUrl":"10.1159/pat/aehag002","url":null,"abstract":"<p><p>Introduction Squamous cells are a rare finding in the thyroid gland and have been reported in a wide range of entities, from benign cysts to carcinomas. This study presents the diagnostic outcomes and potential pitfalls associated with squamous cell lesions in the thyroid gland, based on the experience of a tertiary centre's pathology laboratory. The main focus of the present study was on morphology, cytohistological correlation, immunohistochemistry and diagnostic pitfalls. Methods A pathology laboratory's information system was searched for squamous cell findings in the thyroid gland. Cytological samples were classified according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and histological specimens were categorised according to the World Health Organization (WHO) classification. Available microscopy slides were re-examined, and selected immunohistochemical and morphological features were documented. Results Our series included 42 thyroid gland specimens containing squamous cells, comprising 22 cytological samples and 20 histological samples. The most common diagnosis by the Bethesda Category for Thyroid Cytopathology (TBSRTC) was malignant (VI, 50%). According to histologies, most cases were malignant (n = 10, 62.5%), with anaplastic thyroid carcinoma (ATC) being the most frequent diagnosis (n = 5, 31.3%). There was one discordant case in which cytology suggested a benign lesion, whereas histology revealed an ATC. Morphologically, squamous cells in TBSRTC categories V and VI were atypical, and inflammatory infiltrates were more profound. CK5/6 and p40 were positive in all tested squamous cells. Conclusion The presence of squamous cells in thyroid samples can make diagnosis challenging, highlighting the need to correlate findings with clinical information. In this study, disagreements regarding malignancy between cytology and histology occurred in only one of nine cases. Only diagnostic discordance occurred in two out of nine cases.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630833","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}
PathobiologyPub Date : 2026-07-13DOI: 10.1159/000553452
Soohwan Choi, Myungsun Shim, Kyueng-Whan Min, Yung-Kyun Noh, Hyung Suk Kim, Kyu Shik Kim, Un Suk Jung, Kyung Suk Lee, Mi Jung Kwon
{"title":"Activated Cancer-Associated Fibroblasts Are Associated with Immunosuppression and Poor Prognosis in Clear Cell Renal Cell Carcinoma.","authors":"Soohwan Choi, Myungsun Shim, Kyueng-Whan Min, Yung-Kyun Noh, Hyung Suk Kim, Kyu Shik Kim, Un Suk Jung, Kyung Suk Lee, Mi Jung Kwon","doi":"10.1159/000553452","DOIUrl":"10.1159/000553452","url":null,"abstract":"<p><strong>Introduction: </strong>Clear cell renal cell carcinoma (ccRCC) exhibits substantial heterogeneity within its tumor microenvironment, contributing to variable clinical outcomes. The prognostic significance and molecular characteristics of cancer-associated fibroblasts in ccRCC remain poorly defined.</p><p><strong>Methods: </strong>We analyzed 736 ccRCC cases (203 institutional and 533 TCGA) to identify histologically distinct activated cancer-associated fibroblasts (aCAFs; oval to mildly elongated immature fibroblasts occupying >5% of stroma) on H&E-stained slides. Clinicopathological correlations, immunohistochemical immune profiling, transcriptomic analyses, and machine learning-based survival modelling were performed; for the latter, 17 neoadjuvant-treated cases were excluded from the TCGA cohort, yielding an analytic cohort of 516 cases.</p><p><strong>Results: </strong>aCAFs were identified in 12.3% and 12.9% of institutional and TCGA cohorts, respectively, and were significantly associated with advanced tumor stage, higher histologic grade, sarcomatoid features, and poor disease-specific survival, remaining an independent prognostic factor on multivariate analysis. aCAF-positive tumors exhibited reduced tumor-infiltrating lymphocytes and CD4+ T-cell infiltration, enhanced TGF-β signaling, and molecular enrichment in FGFR2 and complement regulation pathways. In machine learning-based survival models, aCAFs ranked among the top five prognostic predictors, and their inclusion improved predictive accuracy with DSS AUC of 0.874 versus 0.858. In silico drug screening identified ponatinib and HG6-64-1 as candidate therapeutic agents for tumors with high fibroblast activation protein-α expression.</p><p><strong>Conclusion: </strong>Morphologically defined aCAFs represent a histologically recognizable and clinically meaningful stromal component associated with immunosuppression and adverse prognosis in ccRCC, with potential utility for routine diagnostic application and therapeutic targeting.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437549","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}
PathobiologyPub Date : 2026-07-07DOI: 10.1159/000553407
Seon Ung Kim, Youn Soo Lee, Sin-Soo Jeun, Jae-Sung Park, Donghyuk Lee, Jun Kang
{"title":"Targeted Next-Generation Sequencing-Based Mutational Signature Analysis in Hypermutated Gliomas: A Case-Centered Feasibility Assessment.","authors":"Seon Ung Kim, Youn Soo Lee, Sin-Soo Jeun, Jae-Sung Park, Donghyuk Lee, Jun Kang","doi":"10.1159/000553407","DOIUrl":"10.1159/000553407","url":null,"abstract":"<p><strong>Introduction: </strong>Gliomas generally display a low tumor mutational burden (TMB) and an immunosuppressive microenvironment, both of which restrict the effectiveness of immune checkpoint inhibitors. However, certain gliomas acquire a high TMB, which may arise either due to temozolomide (TMZ) therapy or mismatch repair deficiency. Mutational signature analysis identifies specific somatic mutation patterns, providing insight into underlying mutational mechanisms. This study provides a case-centered feasibility assessment of mutational signature refitting from a clinically implemented targeted next-generation sequencing (NGS) panel in two hypermutated gliomas identified within a real-world glioma testing cohort.</p><p><strong>Methods: </strong>Twenty-eight gliomas tested using the Oncomine Comprehensive Assay Plus NGS panel in routine clinical practice were retrospectively reviewed. Panel-derived TMB was used for coarse stratification and to identify hypermutated tumors for detailed mutational signature interpretation. Mutational signature refitting was performed using Signature Analyzer for Targeted Sequencing.</p><p><strong>Results: </strong>Two gliomas exhibited elevated panel-derived TMB estimates: one after TMZ therapy and another in association with MSH2 deficiency. The remaining 26 non-hypermutated tumors had sparse mutation counts, limiting reliable signature interpretation. COSMIC single-base substitution signature 11 (SBS11) was predominant in the TMZ-treated hypermutated glioma, whereas the MSH2-deficient glioma demonstrated increased SBS1 and SBS26.</p><p><strong>Conclusion: </strong>This real-world, case-centered study suggests that targeted-panel mutational signature refitting may provide complementary molecular context in selected hypermutated gliomas. The observed patterns were concordant with prior TMZ exposure or mismatch repair deficiency. However, in non-hypermutated tumors, sparse mutation counts limited reliable signature interpretation, and the clinical impact of this approach remains to be established.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405316","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}
PathobiologyPub Date : 2026-06-19DOI: 10.1159/000553118
Ayana Suzuki, Mitsuyoshi Hirokawa, Hidetaka Yamamoto, Takuya Higashiyama, Takashi Akamizu
{"title":"Solitary Fibrous Tumor Arising in Thyroid Follicular Nodular Disease: A Case Report.","authors":"Ayana Suzuki, Mitsuyoshi Hirokawa, Hidetaka Yamamoto, Takuya Higashiyama, Takashi Akamizu","doi":"10.1159/000553118","DOIUrl":"10.1159/000553118","url":null,"abstract":"<p><strong>Introduction: </strong>Herein, we present the first documented case of a solitary fibrous tumor (SFT) arising within thyroid follicular nodular disease and discuss its histogenesis.</p><p><strong>Case presentation: </strong>A man in his 60s presented with a left thyroid nodule. Histologically, the nodule was composed of spindle cells and thyroid follicles. The spindle cells were positive for CD34 and STAT6, negative for PAX8 and cytokeratin, and harbored a NAB2::STAT6 fusion, confirming the diagnosis of SFT. No extrathyroidal SFT was identified, and the Demicco model classified the tumor as low risk.</p><p><strong>Conclusion: </strong>This report suggests that SFT may arise de novo within the stromal component of thyroid follicular nodular disease. This underscores the need to consider SFT in the differential diagnosis of spindle-cell lesions occurring within thyroid nodules.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284173","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}
PathobiologyPub Date : 2026-06-05DOI: 10.1159/000552283
Boglárka Pósfai, Anna Jakab, Alex Jenei, Katalin Dezső, Tamás László, Attila Fintha, Tamás Micsik, Csaba Bödör, Gertrúd Forika, Áron Somorácz, Borbála Dénes, Dávid Semjén, Kornélia Eizler, Nándor Giba, Zsombor Melegh, Helga Engi, Ali Bassam, László Torday, Anikó Maráz, Krisztián Nagyiványi, Lajos Géczi, Zsófia Küronya, Krisztina Bíró, Ondrej Hes, Kristyna Pivovarcikova, Henriett Butz, Attila Patócs, Fanni Sánta, Levente Kuthi
{"title":"Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Multicentric Comprehensive Clinical, Pathological, and Molecular Analysis of 12 Cases.","authors":"Boglárka Pósfai, Anna Jakab, Alex Jenei, Katalin Dezső, Tamás László, Attila Fintha, Tamás Micsik, Csaba Bödör, Gertrúd Forika, Áron Somorácz, Borbála Dénes, Dávid Semjén, Kornélia Eizler, Nándor Giba, Zsombor Melegh, Helga Engi, Ali Bassam, László Torday, Anikó Maráz, Krisztián Nagyiványi, Lajos Géczi, Zsófia Küronya, Krisztina Bíró, Ondrej Hes, Kristyna Pivovarcikova, Henriett Butz, Attila Patócs, Fanni Sánta, Levente Kuthi","doi":"10.1159/000552283","DOIUrl":"10.1159/000552283","url":null,"abstract":"<p><strong>Introduction: </strong>Fumarate hydratase-deficient renal cell carcinoma (FHd RCC) is a rare, aggressive subtype of kidney cancer associated with hereditary leiomyomatosis and renal cell carcinoma syndrome.</p><p><strong>Methods: </strong>We retrospectively analyzed 12 FHd RCC cases from Hungarian patients, assessing clinical, histopathological, immunohistochemical, and molecular features.</p><p><strong>Results: </strong>The median age at diagnosis was 48.5 years, with a male-to-female ratio of 1.6:1. Most patients presented symptomatically and in an advanced stage; ten underwent surgery, and seven had metastatic disease at diagnosis. Tumors were unifocal, unilateral, and high-grade, displaying heterogeneous architectural patterns, often with eosinophilic cytoplasm and prominent viral inclusion-like nucleoli. Fumarate hydratase (FH) expression was lost in all but 1 tumor, while aberrant nuclear and cytoplasmic 2SC positivity was observed in all cases. CK7 was consistently negative, whereas AMACR and PAX8 were positive in all tested tumors. GATA3 expression was focal in 2 tumors. PD-L1 positivity was detected in 4 tumors, including 1 with high tumor mutational burden. Pathogenic FH mutations were confirmed in nine cases, including three germline alterations. Systemic therapy was administered in 7 patients, with variable responses.</p><p><strong>Conclusion: </strong>Our findings highlight the pronounced morphological heterogeneity of FHd RCC and the critical role of combined FH and 2SC immunohistochemistry for accurate diagnosis. FHd RCC should be recognized as a distinct, highly malignant renal neoplasm, warranting comprehensive histological, immunohistochemical, and genetic assessment, along with genetic counseling to identify potential hereditary background.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-15"},"PeriodicalIF":1.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176306","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}
PathobiologyPub Date : 2026-05-22DOI: 10.1159/000552636
Che Liu, Zhengrong Zhou, Tao Zeng, Jianpeng Hu, Huazhong Cai, Pan Huang
{"title":"Lactate and <italic>Akkermansia muciniphila</italic>: Emerging Roles in Inflammatory Bowel Disease and Colorectal Cancer.","authors":"Che Liu, Zhengrong Zhou, Tao Zeng, Jianpeng Hu, Huazhong Cai, Pan Huang","doi":"10.1159/000552636","DOIUrl":"10.1159/000552636","url":null,"abstract":"<p><strong>Background: </strong>Lactate levels are significantly elevated in the tissues of patients with inflammatory bowel disease (IBD) and colorectal cancer (CRC). In IBD, lactate promotes anti-inflammatory repair by inducing M2 macrophage polarization, whereas abnormal lactate levels in the CRC tumor microenvironment contribute to tumor initiation and progression through acidification, immune reprogramming, and activation of pro-angiogenic pathways. Akkermansia muciniphila (Akk) exhibits a distinct preference for lactate as a nutritional substrate, and its abundance increases significantly in the murine gut following lactate administration. As an important intestinal symbiont, Akk shows potential in the prevention and treatment of both IBD and CRC.</p><p><strong>Key messages: </strong>We hypothesize that targeting lactate metabolism and leveraging the active components of Akk may provide novel strategies for the prevention and therapy of IBD and CRC.</p><p><strong>Summary: </strong>This review aims to summarize the relationship among lactate, Akk, and inflammation-associated CRC, thereby offering new perspectives and approaches for the clinical management of CRC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-12"},"PeriodicalIF":1.7,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005988","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}
PathobiologyPub Date : 2026-05-21DOI: 10.1159/000552666
Betül Öğüt, Mehmet Arda İnan, Özgür Ekinci, Meral Toker, Ceren Bilkan Öge, Osman Sütçüoğlu, Mualla İlknur Gündüz, Gülen Akyol
{"title":"Stromal Podoplanin Expression as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.","authors":"Betül Öğüt, Mehmet Arda İnan, Özgür Ekinci, Meral Toker, Ceren Bilkan Öge, Osman Sütçüoğlu, Mualla İlknur Gündüz, Gülen Akyol","doi":"10.1159/000552666","DOIUrl":"10.1159/000552666","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic cancer is known for its poor prognosis, characterized by early systemic dissemination and locally aggressive behavior. Podoplanin (PDPN) is a mucin-type transmembrane glycoprotein physiologically expressed in various tissues. In certain malignancies, overexpression of PDPN has been linked to enhanced tumor invasiveness, metastatic potential, and unfavorable clinical outcomes. In this study, we evaluated stromal PDPN expression in a cohort of patients diagnosed with pancreatic carcinoma and investigated its immunohistochemical profile in relation to patient survival.</p><p><strong>Methods: </strong>This retrospective study included 103 cases of pancreatic ductal adenocarcinoma (PDAC). Histological grade, perineural invasion, pathological tumor stage, lymph node status, and lymphovascular invasion were evaluated. Immunohistochemical expression of PDPN was evaluated as a percentage by calculating the proportion of PDPN-positive (of any staining intensity) tumor stroma relative to the total tumor stromal area.</p><p><strong>Results: </strong>Among 103 cases of PDAC, the median value of immunohistochemical expression of PDPN in tumor stroma was 20%. Complete absence of PDPN expression was observed in 7 patients (6.8%). The survival analysis indicated that higher stromal PDPN expression was associated with shorter overall survival (log-rank p = 0.0129). High PDPN expression in cancer-associated fibroblasts showed a borderline association with overall survival in multivariable Cox regression analysis (hazard ratio: 1.52, 95% confidence interval: 1.00-2.32, p = 0.05).</p><p><strong>Conclusion: </strong>PDPN expression may serve as a prognostic biomarker in PDAC and could contribute to future therapeutic stratification.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988662","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}
PathobiologyPub Date : 2026-04-29DOI: 10.1159/000552286
Claire W Michael, Ben Davidson
{"title":"Cellular Plasticity in Malignant Transformation: Mesothelial Cells.","authors":"Claire W Michael, Ben Davidson","doi":"10.1159/000552286","DOIUrl":"10.1159/000552286","url":null,"abstract":"<p><strong>Background: </strong>Mesothelial proliferations range from reactive lesions to benign and malignant tumors, bearing witness to the plasticity of these cells. Their diagnosis often requires combination of morphological assessment, immunohistochemistry, and molecular testing.</p><p><strong>Summary: </strong>Considerable progress has been made in recent years in all the above aspects. The separation of reactive from neoplastic mesothelial proliferations has become more robust. Mesothelioma in situ is now recognized as precursor of invasive mesothelioma and better tools exist for its differentiation from benign mimics. Differentiating mesothelial tumors from other malignancies, including metastatic carcinomas, sarcomas, and other tumors, is now more easily achieved. Genetic conditions which predispose to development of mesothelioma at a young age have been identified and characterized. These issues are discussed in this review.</p><p><strong>Key messages: </strong>Mesothelial pathology is an evolving field and more knowledge of these processes is likely to be gained in coming years. The diagnosis of these tumors requires experts with subspecialty in cytology, thoracic, soft tissue/bone, and gynecologic pathology, cooperating with surgeons, radiologists, and oncologists at specialized centers.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777792","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}
PathobiologyPub Date : 2026-04-27DOI: 10.1159/000551677
Mariana O Nunes, Diana Luísa Almeida-Nunes, Ana E C de Lima, Verónica Ferreira, Cláudia Lobo, Paula M Monteiro, Sara Carvalho, Miguel Henriques Abreu, Carla Bartosch, Sara Ricardo
{"title":"Tracking Chemotherapy Effects via ALDH1A1, SOX2, CD44v6, and P-gp Expression in Malignant Ascites from High-Grade Serous Carcinoma.","authors":"Mariana O Nunes, Diana Luísa Almeida-Nunes, Ana E C de Lima, Verónica Ferreira, Cláudia Lobo, Paula M Monteiro, Sara Carvalho, Miguel Henriques Abreu, Carla Bartosch, Sara Ricardo","doi":"10.1159/000551677","DOIUrl":"10.1159/000551677","url":null,"abstract":"<p><strong>Introduction: </strong>Malignant ascites is frequently observed in high-grade serous carcinoma (HGSC), yet its value as a dynamic source for molecular profiling across treatment stages remains underexplored. The main aim of this study was to evaluate the feasibility of immunocytochemical analysis of malignant ascites (MA) samples from patients with high-grade serous carcinoma. A goal was to determine whether marker expression varies before and after chemotherapy and between clinical response groups.</p><p><strong>Methods: </strong>A cohort of 37 MA samples from 33 HGSC patients was analysed by immunocytochemistry for ALDH1A1, SOX2, CD44v6, and P-glycoprotein. Full-volume centrifugation of MA (1-4 L) was used to maximize tumour cell recovery. A biomarker profile was considered positive if ≥1 marker showed >10% tumour cell expression.</p><p><strong>Results: </strong>This profile was significantly more frequent in post-chemotherapy samples (72.2%) than in pre-chemotherapy samples (21.1%; p = 0.003). Stratified analysis revealed increased expression in platinum-sensitive patients following chemotherapy (60% vs. 14.3%, p = 0.032), suggesting chemotherapy-induced reprogramming rather than selection alone. Expression of p-glycoprotein was more frequent in resistant cases, though often limited to <25% of tumour cells. Survival analysis showed no significant difference in overall survival between biomarker-positive patients (p = 0.176).</p><p><strong>Conclusion: </strong>Our findings suggest that chemotherapy modulates the expression of cancer stem cells and resistance-related markers in HGSC, potentially contributing to adaptive resistance mechanisms. MA, particularly when processed in full, represents a valuable, minimally invasive source of tumour cells for real-time biomarker monitoring. This approach may support early identification of resistance phenotypes and inform personalized therapeutic strategies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777783","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}