Pathobiology最新文献

{"title":"Advances in Renal Cell Carcinoma Diagnosis: A Review on Biomarkers.","authors":"Agnese Orsatti, Fernanda Fernandes-Pontes, João Ricardo E Silva, Nuno Tiago Tavares, Carmen Jerónimo, Rui Henrique, Ângelo Rodrigues, Costantino Ricci, João Lobo","doi":"10.1159/000550723","DOIUrl":"10.1159/000550723","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is a heterogeneous disease, with the last World Health Organization (WHO) classification introducing several novel entities, among which the molecularly defined RCCs. This growing complexity highlights the need for integration of morphology, immunohistochemistry (IHC) and molecular techniques, ensuring accurate classification and reducing the \"RCC not otherwise specified (NOS) category.\"</p><p><strong>Summary: </strong>Molecular assays such as next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are increasingly necessary for diagnosing molecularly defined RCCs. IHC remains fundamental for diagnosing both \"old\" and newly defined RCCs, representing a surrogate for molecular alterations such as fumarate-hydratase and succinate-dehydrogenase deficiency, anaplastic lymphoma kinase rearrangements, SMARCB1 loss, and TFE3 rearrangements. However, entities like ELOC-mutated RCC require molecular testing for diagnosis. Liquid biopsy offers a further diagnostic tool. Circulating microRNAs can support diagnosis, classification, and monitoring. Furthermore, circulating tumor DNA (ctDNA) methylation analyses and circulating tumor cells (CTCs) offer promising and minimally invasive tools for stratification, though their clinical use is still evolving.</p><p><strong>Key messages: </strong>A precise diagnosis integrating histopathology, IHC, and molecular testing is critical for guiding management, identifying hereditary syndromes, and implementing personalized tumor biology-based therapies. With evolving molecular diagnostic and circulating biomarkers, careful clinical integration is needed to optimize outcomes and treatment.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"263-282"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065897","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}

{"title":"The Human Immunodeficiency Virus Type 1 Budding Machinery: Deconstructing the Endosomal Sorting Complexes Required for Transport-Mediated Scission Pathway.","authors":"Mahmoud M Yaseen, Nizar Abuharfeil","doi":"10.1159/000551438","DOIUrl":"10.1159/000551438","url":null,"abstract":"<p><strong>Background: </strong>The final step of the Human immunodeficiency virus type 1 (HIV-1) replication cycle, virion budding and scission from the host cell membrane, is executed not by a viral enzyme but by the hijacked host endosomal sorting complexes required for transport (ESCRT) machinery.</p><p><strong>Summary: </strong>This review synthesizes current knowledge on how HIV-1 Gag polyprotein recruits and coordinates the ESCRT pathway. We detail the critical roles of the PTAP and YPX_nL late-domain motifs in engaging Tsg101 (ESCRT-I) and ALIX adaptors, which nucleate the assembly of constrictive ESCRT-III polymers and the VPS4 ATPase to catalyze membrane fission. We examine the plasticity of these recruitment pathways, the regulatory influence of ubiquitination, and how cell-type-specific factors impact budding efficiency. Furthermore, we assess emerging connections between ESCRT function, viral pathogenesis, and therapeutic opportunities.</p><p><strong>Key messages: </strong>The ESCRT-dependent budding of HIV-1 is a robust yet vulnerable process, characterized by redundant entry points converging on an essential core scission engine. This mechanistic understanding reveals critical virus-host interfaces that present promising targets for novel antiviral strategies aimed at disrupting this late stage of the viral life cycle.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"296-318"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675366","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}

{"title":"Expression of Far Upstream Element-Binding Protein in Gastrointestinal Stromal Tumors and Its Regulation of Cell Proliferation, Migration, and Invasion.","authors":"Zhigao Zhang, Fucheng Zhang, Shubao Zhang, Xiaoling Song, Yonghong Xu, Yaojun Wang","doi":"10.1159/000547278","DOIUrl":"10.1159/000547278","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to observe the expression of far upstream element-binding protein 1 (FUBP1) in gastrointestinal stromal tumors (GISTs) and explore its impact on the biological behavior of GIST cells.</p><p><strong>Methods: </strong>Fifty patients with GIST who underwent surgical resection were selected, and cancer tissues and adjacent normal tissues were gathered. The expression level of FUBP1 and its correlation with clinicopathological data and prognosis in patients with GISTs were assessed. GIST-T1 cell lines in the logarithmic growth phase were transfected with lentiviruses overexpressing FUBP1, small hairpin RNA targeting FUBP1, and their respective negative controls. FUBP1 expression levels in each group, cell biological behavior were tested, and the effect of FUBP1 on tumor growth in vivo were tested.</p><p><strong>Results: </strong>Compared to adjacent normal tissues, FUBP1 expression level was elevated in GIST cancer tissues and was concerned with tumor size, NIH risk category, and tumor metastasis in patients. Knockdown of FUBP1 inhibited cell malignant behaviors and promoted cell apoptosis, while overexpression of FUBP1 had the opposite effects. FUBP1 facilitated the growth of GIST cells in vivo.</p><p><strong>Conclusion: </strong>FUBP1 is upregulated in GISTs and facilitates the invasion, migration, and proliferation of GIST cells. This provides a new perspective for understanding the pathogenesis of GIST and lays a foundation for developing potential therapeutic strategies targeting FUBP1.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"23-33"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964272","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}

{"title":"The Power of MUC2 in Mucinous Adenocarcinomas.","authors":"Kemal Behzatoğlu","doi":"10.1159/000550592","DOIUrl":"10.1159/000550592","url":null,"abstract":"<p><p><p>Background: In cancers, key prognostic determinants such as clinical stage and mutational load are well recognized. However, mucinous adenocarcinomas (MACs) display distinct biological behavior as a large proportion of their tumor volume consists of extracellular mucin, predominantly the MUC2 protein, rather than neoplastic cells. MUC2 provides a protective barrier for cancer cells against external factors, including chemotherapeutic agents and cytotoxic lymphocytes, while its anti-inflammatory and tumor-suppressive properties paradoxically support tumor persistence and immune evasion. Summary: Excessive mucin secretion and its viscoelastic properties facilitate rapid local expansion and dissemination into adjacent tissues. These effects are particularly significant in organs that open into body cavities, such as the colon and appendix, whereas they are less pronounced in confined organs such as the breast. In ductal organs, overexpression of MUC2 may promote early invasion through pressure-induced disruption of ductal structures. Key Messages: Consequently, in MACs, tumor location and organ architecture, alongside clinical stage and mutational profile, are critical determinants of biological behavior. Accurate differential diagnosis and therapeutic approaches should address both organ-specific pathways and MUC2-related mechanisms, including its structural, anti-inflammatory, and tumor-suppressive functions. MUC2-targeted therapies may thus represent a promising adjunct to conventional, organ-based treatment strategies. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"232-245"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011577","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}

{"title":"Increased Infiltration of Tissue-Resident Memory T Cells Predicts a Good Response to Anti-PD-L1 Immunotherapy in Extrahepatic Cholangiocarcinoma.","authors":"Yoshiyuki Tagayasu, Rin Yamada, Kosuke Kanemitsu, Yoshihiko Kondo, Yukio Fujiwara, Takumi Tanizaki, Rumi Itoyama, Yuki Kitano, Hiromitsu Hayashi, Yoshihiro Komohara, Masaaki Iwatsuki","doi":"10.1159/000547222","DOIUrl":"10.1159/000547222","url":null,"abstract":"<p><strong>Introduction: </strong>Extrahepatic cholangiocarcinoma (eCCA) is an aggressive malignancy with a poor prognosis. Immune checkpoint inhibitors (ICIs) targeting PD-L1 enhance antitumor immunity, but reliable predictive biomarkers remain unclear. This study investigated tumor-infiltrating immune cells, including T cells and macrophages, as potential biomarkers for ICI efficacy in eCCA.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 15 eCCA patients who received durvalumab for recurrent or unresectable disease after surgery. Immunohistochemical staining assessed PD-L1, HLA-class I/II, CD8, and CD103 expression in resected tumor specimens. ICI response was evaluated using RECIST 1.1 criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Correlations between immune cell infiltration and clinical outcomes were analyzed.</p><p><strong>Results: </strong>Five patients achieved PR, five SD, and five PD. CD8+ and CD103+ T-cell infiltration within tumor nests was significantly higher in PR and SD groups than in PD (p = 0.032, p = 0.0147). High HLA-class I expression correlated with response, while PD-L1 and HLA-class II showed no significant association. Patients with increased CD8+CD103+ T cells demonstrated better disease control.</p><p><strong>Conclusion: </strong>Intratumoral CD8+ and CD103+ T cells may serve as predictive biomarkers for ICI efficacy in eCCA, highlighting tissue-resident immune cells as therapeutic targets.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732642","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}

{"title":"Expression of ENPP1 in Testicular Germ Cell Tumors: Exploring Its Role in the Pathobiology of Distinct Histotypes and in Prognosis.","authors":"Miguel Bernardo Alves, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Alexandra Lapa, Rita Guimarães, Paula Lopes, Isaac Braga, Joaquina Maurício, Carmen Jerónimo, Rui Henrique, João Lobo","doi":"10.1159/000547655","DOIUrl":"10.1159/000547655","url":null,"abstract":"<p><strong>Introduction: </strong>Testicular germ cell tumors (TGCTs) are the most common solid malignancies among young men. Despite good response to cisplatin-based chemotherapy, side effects negatively affect quality of life. Recent development of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors opens opportunity for targeted therapy, but ENPP1 expression in TGCTs has not been characterized. We aimed to assess ENPP1 immunoexpression in a cohort of primary and metastatic TGCTs, and in normal testicular parenchyma, looking into differential immunoexpression patterns among subtypes and clinicopathological correlations.</p><p><strong>Methods: </strong>Overall, 90 TGCT individual tumor components from 63 patients diagnosed and treated at a comprehensive cancer center were assessed, using immunohistochemistry to ascertain biomarker expression (combined score of stained tumor cells percentage and intensity). In silico analysis of The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) datasets was performed for additional validation.</p><p><strong>Results: </strong>Significant differences in ENPP1 expression across TGCT subtypes were disclosed. Seminomas and embryonal carcinomas (ECs) showed significantly higher ENPP1 expression compared to other subtypes, the highest levels being found in EC, which was confirmed with in silico analysis of TCGA and HPA. Expression in metastatic samples was overall lower compared to primary TGCTs. ENPP1 was not expressed in germ cells of healthy testicular parenchyma.</p><p><strong>Conclusion: </strong>We demonstrate that ENPP1 is expressed in TGCTs, mostly EC (a frequently aggressive tumor subtype), followed by seminoma (the most common TGCT subtype), suggesting potential responsiveness to novel ENPP1 inhibitors. Absent expression in germ cells of healthy testicular parenchyma suggest cancer cells specificity and low probability of fertility-related toxicity.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"12-22"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732641","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}

{"title":"Mechanistic Underpinnings of Lung Cancer Initiation in Patients with Human Immunodeficiency Virus Infection.","authors":"Omar Bushara, Charles Crepy D Apos Orleans, Yash Kadakia, Rucha Alur, David DeVaro, Sunil Singhal","doi":"10.1159/000546745","DOIUrl":"10.1159/000546745","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading cause of cancer related death in the USA. A proven risk factor for the development and progression of lung cancer is human immunodeficiency virus (HIV).</p><p><strong>Summary: </strong>HIV persists within the lung in alveolar macrophages and bronchial epithelial cells, reducing mucociliary function and decreasing epithelial integrity. This persistence yields chronic inflammation by way of matrix metalloproteinases, which causes pulmonary injury. Over time, this progresses to pulmonary disease and allows for the development of superimposed pulmonary infections and chronic inflammatory states. This injury is a risk factor for the development of dysplasia, and chronic pulmonary disease and infections further increase the risk for developing lung cancer. HIV persistence and chronic inflammation also lead to CD8+ T cell exhaustion and alterations to macrophages and dendritic cells that blunt the physiologic antitumor response. As such, HIV infection promotes initial dysplasia and allows for progression on preinvasive lesions to frank malignancy.</p><p><strong>Key messages: </strong>The purpose of this review is to highlight HIV as an under-appreciated risk factor and summarize the biologic and immunologic role of HIV in lung cancer initiation and progression. Further research regarding risk reduction and surveillance in this population and the potential increased role of immunotherapy is warranted.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"48-62"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732643","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}

{"title":"ThinPrep® Whole-Slide Digital Images versus Conventional Microscopy in Negative for Intraepithelial Lesion or Malignancy, Atypical Squamous Cells of Undetermined Significance, and Low-Grade Squamous Intraepithelial Lesion Cervical Lesions: European Federation of Cytological Societies (EFCS) Study.","authors":"Ester Puntonen, Sara Bazzon, Massimo Bongiovanni, Rosario Granados, Ines Krivak Bolanca, Maria Nasioutziki, Maurizio Pinamonti, Danijela Vrdoljak-Mozetic, Arrigo Capitanio, Beatrix Cochand-Priollet, Ambrogio Fassina, Giovanni Negri, Laura Ventura, Ivana Kholová","doi":"10.1159/000550455","DOIUrl":"10.1159/000550455","url":null,"abstract":"<p><strong>Introduction: </strong>High inter- and intraobserver variability is acknowledged in negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), and low-grade squamous intraepithelial lesion (LSIL) diagnostic categories in cervical cytology. As digital cytology has emerged, whole-slide images (WSIs) have been compared to conventional light microscopy (LM) to evaluate its feasibility in routine practice.</p><p><strong>Methods: </strong>Six cytopathologists evaluated 20 liquid-based cervical samples diagnosed as ASC-US, LSIL, or NILM with known hrHPV status, both by conventional LM and WSI, equalling 240 evaluations. Interobserver agreement was measured using Fleiss's kappa, Kendall´s coefficient and interclass correlation (ICC).</p><p><strong>Results: </strong>Most of the samples (93.75%) were assigned to the same original range of categories: NILM 5 (25%), ASC-US 10 (50%), and LSIL 5 (25%). WSI versus LM interobserver agreement varied with Fleiss's kappa (0.324 versus 0.319), Kendall's W (0.670 versus 0.572), and ICC (0.585 versus 0.414). Interobserver agreement for the ASC-US category was higher in Kendall's W (0.435 for WSI versus 0.329 for LM) and in ICC (0.394 versus 0.118). Fleiss's kappa showed lower interobserver agreement for ASC-US in WSI than LM (0.000 versus 0.039).</p><p><strong>Conclusion: </strong>This study illustrated that despite overall better agreement in WSI, ASC-US results were less favourable in WSI than LM, according to Fleiss's kappa test, but not other tests.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"221-231"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011553","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}

{"title":"Aberrant Cytoplasmic p53 Expression and Its Correlation with <italic>TP53</italic> Mutation Status and Functional Implications in Stage II and III Colorectal Cancer.","authors":"Meejeong Kim, Lingyan Jin, Hye-Yeong Jin, Nam-Yun Cho, Saewon Han, Tae-You Kim, Jeong Mo Bae, Gyeong Hoon Kang, Younghoon Kim","doi":"10.1159/000548104","DOIUrl":"10.1159/000548104","url":null,"abstract":"<p><strong>Introduction: </strong>TP53 mutation is frequently observed in colorectal cancer (CRC) and is often linked to associated with immunohistochemical p53 expression patterns. Recent studies have identified cytoplasmic p53 expression in CRC, but its correlation with TP53 mutation domains and functional properties remains unclear.</p><p><strong>Methods: </strong>We evaluated nuclear and cytoplasmic p53 staining patterns in 429 stage II and III CRC samples. TP53 mutation status was assessed using targeted next-generation sequencing. Correlations among cytoplasmic expression, mutation domains, functional properties, and clinicopathological features were analyzed.</p><p><strong>Results: </strong>Cytoplasmic p53 expression was detected in 21 (4.9%) CRCs. All cytoplasmic expressions were accompanied by nuclear staining. TP53 mutations associated with cytoplasmic p53 predominantly involved nonsense mutations within the tetramerization domain (TD, 61.9%) and nuclear localization signals (NLSs, 14.3%). All functionally characterized mutations associated with cytoplasmic p53 exhibit loss-of-function (LOF) without gain-of-function or dominant-negative effects. NLS and TD mutations were significantly associated with BRAF V600E mutation but not with microsatellite instability status.</p><p><strong>Conclusion: </strong>Aberrant cytoplasmic p53 expression in CRC leads to nonsense mutations in the TD and NLS domains of TP53. These mutations exclusively induced LOF characteristics. Cytoplasmic expression patterns differ functionally and molecularly from classical nuclear staining patterns, highlighting the need for novel interpretation criteria for p53 immunostaining.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"63-71"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964274","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}

{"title":"Significantly Decreased Progesterone Receptor Expression in Corded and Hyalinized Variant of Endometrioid Adenocarcinoma: A Potential Cause of Resistance to Progestin Treatment.","authors":"Uiree Jo, Bong-Hee Park, Chang Ohk Sung, Kyu-Rae Kim","doi":"10.1159/000549857","DOIUrl":"10.1159/000549857","url":null,"abstract":"<p><strong>Introduction: </strong>The corded and hyalinized variant of endometrioid adenocarcinoma (CHEC) is a biphasic tumor composed of cords of epithelioid and/or spindle cells (CoES) within hyalinized or chondroid stroma, which is often misdiagnosed as carcinosarcoma. CHEC predominantly occurs in younger women, and it has a favorable clinical outcome. Thus, many patients wish to preserve their fertility and undergo conservative treatment. This study investigated a selective loss of progesterone receptor (PR) in the CoES component and reported clinical, histopathological, and immunohistochemical features of CHEC.</p><p><strong>Methods: </strong>A total 6 patients with CHEC between 2004 and 2021 were searched. We performed immunohistochemistry for estrogen receptor (ER), PR, β-catenin, E-cadherin, cytokeratin, p53, and Ki-67.</p><p><strong>Results: </strong>The patients were 21-40 years old. All of the tumors were FIGO grade 1 endometrioid adenocarcinoma (EAC) intermingled with CoES component. Notably, PR expression was completely lost in the CoES component in contrast to the EAC component, with a significantly different expression pattern of cytokeratin, ER, β-catenin, and E-cadherin from the areas of typical EAC. Four of the 6 patients initially received exogenous progestin treatment, and two of them ultimately had a hysterectomy after progestin treatment. All 4 patients treated with progestin had persistent tumors at the last follow-up curettage or hysterectomy.</p><p><strong>Conclusion: </strong>Considering the usual high rate of complete remission with progestin treatment in patients with EAC, the high rate of persistent tumors in our case series suggests that CHEC may be intrinsically resistant to progestin treatment due to the lack of expression of PR in the CoES component.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"212-220"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086567","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}