PathobiologyPub Date : 2024-01-01Epub Date: 2023-11-07DOI: 10.1159/000534889
Maximilian Bernhardt, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken
{"title":"Exploration of the Tumour Biological Significance of PCLO in Gastric Cancer: Results from a Large Central European Cohort.","authors":"Maximilian Bernhardt, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken","doi":"10.1159/000534889","DOIUrl":"10.1159/000534889","url":null,"abstract":"<p><strong>Introduction: </strong>A recent multiregional whole-exome sequencing of 48 tumour samples from 9 gastric adenocarcinomas discovered PCLO mutations in 23 (47.9%) tumour samples. Based on that unexpected high prevalence of PCLO mutations, we hypothesized a tumour biological significance of PCLO in gastric cancer (GC).</p><p><strong>Methods: </strong>Tumour samples (whole tissue sections) obtained from 466 patients resected for therapy-naive GC were stained with an anti-PCLO antibody. The histoscore for tumour cells and the presence of immunostaining of stromal cells and tumour vessels was documented for each case. An algorithm for PCLO immunopositivity was formed and correlated with clinicopathological patient characteristics.</p><p><strong>Results: </strong>175 GCs were classified as PCLO positive within tumour cells, and 291 as negative. Stromal cells were positive for PCLO in 106 cases and tumour vessels in 84. PCLO-positive GCs more often showed an intestinal phenotype, a lower T category and were more commonly associated with Helicobacter pylori infection. A separate analysis of PCLO expression in intestinal and diffuse type GCs, respectively, showed no significant correlations. Patients with PCLO negative/low tumour cells showed a shortened overall (14.0 ± 1.4 vs. 16.0 ± 1.8 months) and tumour-specific survival (15.0 ± 1.6 months vs. 17.9 ± 3.6). Comparison of PCLOs genotype with its phenotype in 48 tumour samples obtained from nine cases showed no direct correlations with missense mutations.</p><p><strong>Conclusion: </strong>Our data provide evidence that PCLO is differentially expressed in GC and might delay tumour progression.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"187-195"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11126201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484696","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 : 2024-01-01Epub Date: 2024-05-08DOI: 10.1159/000539239
Florian Piques, Martin Penicaud, Wassim Essamet, Simon Cabello-Aguilar, Aude Trinquet, Julie A Vendrell, Valérie Costes, Jérôme Solassol
{"title":"Expanding the Spectrum of Sarcoma with an Internal Tandem Duplication of BCOR: A Non-Pediatric Nasosinusal Case.","authors":"Florian Piques, Martin Penicaud, Wassim Essamet, Simon Cabello-Aguilar, Aude Trinquet, Julie A Vendrell, Valérie Costes, Jérôme Solassol","doi":"10.1159/000539239","DOIUrl":"10.1159/000539239","url":null,"abstract":"<p><strong>Introduction: </strong>Undifferentiated small round-cell sarcomas with BCL6 corepressor (BCOR) alterations, such as an internal tandem duplication (ITD) within exon 15, are typically described as a pediatric group of Ewing-like small round-cell sarcomas.</p><p><strong>Case presentation: </strong>In contrast to this notion, we report the case of a 71-year-old woman with a nasosinusal sarcoma featuring a BCOR ITD. To the best of our knowledge, this presence had not been previously documented in a sarcoma of the nasal and sinus cavities in an elderly patient. The identified duplication shares a similar minimal critical region as described in clear-cell sarcomas of the kidney in children. This alteration, located within the PCGF1 binding domain, is believed to disrupt the activity of PRC1.1.</p><p><strong>Conclusion: </strong>This case underscores the need for in-depth research into the molecular biology of these rare tumors and explores potential alternative treatment options. The patient achieved remission after two cycles of doxorubicin and cyclophosphamide chemotherapy, highlighting the promise of potential therapeutic options for BCOR ITD sarcomas.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"370-374"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892194","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 : 2024-01-01Epub Date: 2024-06-11DOI: 10.1159/000539564
Roshni Patel, Lutfi H Alfarsi, Rokaya El-Ansari, Brendah K Masisi, Busra Erkan, Ali Fakroun, Ian O Ellis, Emad A Rakha, Andrew R Green
{"title":"ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer.","authors":"Roshni Patel, Lutfi H Alfarsi, Rokaya El-Ansari, Brendah K Masisi, Busra Erkan, Ali Fakroun, Ian O Ellis, Emad A Rakha, Andrew R Green","doi":"10.1159/000539564","DOIUrl":"10.1159/000539564","url":null,"abstract":"<p><strong>Introduction: </strong>ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated.</p><p><strong>Methods: </strong>ATF4 expression was evaluated at genomic and transcriptomic levels using METABRIC (n = 1,980), GeneMiner (n = 4,712), and KM-Plotter datasets. Proteomic expression was assessed via immunohistochemistry (n = 2,225) in the Nottingham Primary Breast Cancer Series. ATF4 genomic copy number (CN) variation and mRNA/protein in association with clinicopathological parameters, amino acid transporters (AATs), and patient outcome were investigated.</p><p><strong>Results: </strong>Genomic, transcriptomic, and proteomic overexpression of ATF4 was associated with more aggressive ER-negative tumours. ATF4 mRNA and protein expression were significantly associated with increased expression of glutamine related AATs including SLC1A5 (p < 0.01) and SLC7A11 (p < 0.02). High ATF4 and SLC1A5 protein expression was significantly associated with shorter breast cancer-specific survival (p < 0.01), especially in ER+ tumours (p < 0.01), while high ATF4 and SLC7A11 protein expression was associated with shorter survival (p < 0.01).</p><p><strong>Conclusion: </strong>These findings suggest a complex interplay between ATF4 and AATs in breast cancer biology and underscore the potential role for ATF4 as a prognostic marker in ER+ breast cancer, offering a unique opportunity for risk stratification and personalized treatment strategies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"411-421"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306502","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":"Establishment and Characterization of Salivary Gland-Specific Injury in Transgenic Mice Model.","authors":"Daisuke Omagari, Ryoko Ushikoshi-Nakayama, Tomoe Yamazaki, Hiroko Inoue, Kana Bando, Naoyuki Matsumoto, Ichiro Saito","doi":"10.1159/000539967","DOIUrl":"10.1159/000539967","url":null,"abstract":"<p><strong>Introduction: </strong>Many mouse models for autoimmune diseases also have lesions in non-target organs, which may make it difficult to determine whether the target organ lesion is primary or secondary. Hyposalivation has conventionally been studied using genetically modified mouse models for Sjogren's syndrome as well as spontaneous autoimmune mice with systemic lesions, none of which has salivary gland-specific injury.</p><p><strong>Methods: </strong>In this study, we established a salivary gland-specific injury mouse model using the toxin receptor-mediated cell knockout (TRECK) system by gene modification with the transgene composed of the 5' untranslated region of human salivary mucin gene MUC7 (highly expressed specifically in human salivary gland) inserted at the upstream of hHB-EGF (diphtheria toxin receptor) in the TRECK vector.</p><p><strong>Results: </strong>In this transgenic mouse model, we confirmed salivary gland-specific expression of hHB-EGF gene, and hyposalivation after treatment with diphtheria toxin. Histological assessment of the salivary gland from these mice showed granular convoluted tubule epithelial cells destruction at the same position as a positivity in TUNEL assay.</p><p><strong>Conclusion: </strong>This transgenic mouse model may become a useful tool for elucidating the mechanisms involved in hyposalivation and for developing pharmaceuticals and tissue regenerative medical products for this condition.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"434-441"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760281","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":"Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling.","authors":"Min-Cheng Su, Ching-Hsiang Hsu, Ko-Chen Chen, Jun-Ru Lin, Huei-Ying Li, Yi-Ting Fang, Ruby Yun-Ju Huang, Yung-Ming Jeng","doi":"10.1159/000539612","DOIUrl":"10.1159/000539612","url":null,"abstract":"<p><strong>Introduction: </strong>The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma.</p><p><strong>Methods: </strong>We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal cancer (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC.</p><p><strong>Results: </strong>Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities.</p><p><strong>Conclusion: </strong>These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"393-410"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237299","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 : 2024-01-01Epub Date: 2024-07-17DOI: 10.1159/000540029
Natthawadee Laokulrath, Esther Chuwa, Mihir Gudi, Puay Hoon Tan
{"title":"Low-Grade Adenosquamous Carcinoma of the Breast Masquerading as a Fibroepithelial Lesion on Core Biopsy: A Challenging Case.","authors":"Natthawadee Laokulrath, Esther Chuwa, Mihir Gudi, Puay Hoon Tan","doi":"10.1159/000540029","DOIUrl":"10.1159/000540029","url":null,"abstract":"<p><strong>Introduction: </strong>Diagnosing low-grade adenosquamous carcinoma (LGASC) presents significant challenges due to its subtle morphology, variable immunohistochemical expression, and resemblance to benign lesions like radial scar and complex sclerosing lesions.</p><p><strong>Case presentation: </strong>We present a case of a 53-year-old woman with a subareolar mass initially thought to be a fibroepithelial neoplasm on core biopsy. Subsequent wide excision revealed LGASC with oestrogen receptor expression (weak to moderate intensity, 40% of tumour cells).</p><p><strong>Conclusion: </strong>These findings, rarely reported, highlight the difficulty of diagnosing LGASC on small tissue samples.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"455-462"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477236","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 : 2024-01-01Epub Date: 2023-11-14DOI: 10.1159/000535201
Philipp Joachim Stenzel, Mario Schindeldecker, Larissa Seidmann, Esther Herpel, Markus Hohenfellner, Gencay Hatiboglu, Sebastian Foersch, Stefan Porubsky, Stephan Macher-Goeppinger, Wilfried Roth, Katrin Elisabeth Tagscherer
{"title":"CD15 Is a Risk Predictor and a Novel Target in Clear Cell Renal Cell Carcinoma.","authors":"Philipp Joachim Stenzel, Mario Schindeldecker, Larissa Seidmann, Esther Herpel, Markus Hohenfellner, Gencay Hatiboglu, Sebastian Foersch, Stefan Porubsky, Stephan Macher-Goeppinger, Wilfried Roth, Katrin Elisabeth Tagscherer","doi":"10.1159/000535201","DOIUrl":"10.1159/000535201","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor cells use adhesion molecules like CD15 or sialylCD15 (sCD15) for metastatic spreading. We analyzed the expression of CD15 and sCD15 in clear cell renal cell carcinoma (ccRCC) regarding prognosis.</p><p><strong>Methods: </strong>A tissue microarray containing tissue specimens of 763 patients with ccRCC was immunohistochemically stained for CD15 and sCD15, their expression quantified using digital image analysis, and the impact on patients' survival analyzed. The cell lines 769p and 786o were stimulated with CD15 or control antibody in vitro and the effects on pathways activating AP-1 and tumor cell migration were examined.</p><p><strong>Results: </strong>ccRCC showed a broad range of CD15 and sCD15 expression. A high CD15 expression was significantly associated with favorable outcome (p < 0.01) and low-grade tumor differentiation (p < 0.001), whereas sCD15 had no significant prognostic value. Tumors with synchronous distant metastasis had a significantly lower CD15 expression compared to tumors without any (p < 0.001) or with metachronous metastasis (p < 0.01). Tumor cell migration was significantly reduced after CD15 stimulation in vitro, but there were no major effects on the activating pathways of AP-1.</p><p><strong>Conclusion: </strong>CD15, but not sCD15, qualifies as a biomarker for risk stratification and as an interesting novel target in ccRCC. Moreover, the data indicate a contribution of CD15 to metachronous metastasis. Further research is warranted to decipher the intracellular pathways of CD15 signaling in ccRCC in order to characterize the CD15 effects on ccRCC more precisely.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"219-229"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591957","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 : 2024-01-01Epub Date: 2024-02-08DOI: 10.1159/000536638
Rahul Deb, Natthawadee Laokulrath, Leena Chagla, Puay Hoon Tan
{"title":"Challenges and Clinical Relevance of Modern Breast Pathology Reporting: Your Questions Answered.","authors":"Rahul Deb, Natthawadee Laokulrath, Leena Chagla, Puay Hoon Tan","doi":"10.1159/000536638","DOIUrl":"10.1159/000536638","url":null,"abstract":"<p><strong>Background: </strong>Breast pathology reporting, especially for breast cancer, has evolved through the years, from terse succinct diagnostic conclusions with scant histological details to the current comprehensive reporting guidelines issued by major pathology colleges and bodies, including the International Collaboration on Cancer Reporting. Pathology elements included in reporting guidelines are evidence based and contribute significantly to individualised and personalised patient management.</p><p><strong>Summary: </strong>This article is based on the lively interactive question and answer session that followed the breast pathology segment in the symposium jointly organised by the British Association of Urological Pathology, British Association of Gynaecological Pathologists, British Society of Gastroenterology and the Association of Breast Pathology, in November 2022, titled \"Personalised histopathology reporting for personalised medicine.\"</p><p><strong>Key messages: </strong>The breast pathology session emphasised the clinical utility of breast pathology data items, incorporating a case-based approach by highlighting the relevance of pathology information in various clinical scenarios. This review included clinico-pathological discussion points on florid lobular carcinoma in situ, atypical apocrine adenosis, post-neoadjuvant chemotherapy reporting, atypical ductal hyperplasia presenting at the margin, flat epithelial atypia versus columnar cell change, papilloma on core needle biopsy, margin status, mucocele-like lesion, total duct excision/microdochectomy specimen, and anterior and nipple margins in skin-sparing mastectomy. Effective communication and regular involvement of pathologists in breast multidisciplinary tumour boards are crucial.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"299-312"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707417","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 : 2024-01-01Epub Date: 2023-06-27DOI: 10.1159/000531695
Ricella Souza da Silva, Eduardo M Queiroga, Cynthia de Toledo Osório, Karin S Cunha, Fabiana P Neves, Julieth P Andrade, Eliane P Dias
{"title":"Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression.","authors":"Ricella Souza da Silva, Eduardo M Queiroga, Cynthia de Toledo Osório, Karin S Cunha, Fabiana P Neves, Julieth P Andrade, Eliane P Dias","doi":"10.1159/000531695","DOIUrl":"10.1159/000531695","url":null,"abstract":"<p><strong>Introduction: </strong>The characterization of tumor microenvironment (TME) related factors and their impact on tumor progression have attracted much interest. We investigated cancer cells and cancer-associated fibroblasts (CAFs) to evaluate biomarkers that are associated with neoplastic progression, observing them in different interface zones of colorectal cancer.</p><p><strong>Methods: </strong>On 357 CRC tissue microarrays, using immunohistochemistry, we examined the associations of podoplanin and α-SMA expressed in cancer cells and CAFs and evaluated them in different areas: tumor core, invasive front, tumor budding, tumor-stroma ratio (TSR) scoring, and desmoplastic stroma.</p><p><strong>Results: </strong>CAFs expressing α-SMA were found in more than 90% of the cases. Podoplanin+ was detected in cancer cells and CAFs, with positivities of 38.6% and 70%, respectively. Higher α-SMA+ CAFs and podoplanin+ cancer cells were observed predominantly at the TSR score area: 94.3% and 64.3% of cases, respectively. The status of podoplanin in CAFs+ was higher in the desmoplastic area (71.6%). Stroma-high tumors showed increased expression of α-SMA and podoplanin in comparison with stroma-low tumors. The status of podoplanin in cancer cells was observed in association with lymphatic invasion and distant metastasis.</p><p><strong>Conclusion: </strong>The substance of the CRC was composed predominantly of the surrounding stroma-α-SMA+ CAFs. Podoplanin expressed in the prognosticator zones was associated with unfavorable pathological features. The combination of histologic and protein-related biomarkers can result in a tool for the stratification of patients with CRC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"99-107"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9695916","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 : 2024-01-01Epub Date: 2023-10-10DOI: 10.1159/000533912
Ilias P Nikas, Sojung Lim, Seock-Ah Im, Kyung-Hun Lee, Dae-Won Lee, Hyebin Lee, Han Suk Ryu
{"title":"Discrepancies in Hormone Receptor and HER2 Expression between Malignant Serous Effusions and Paired Tissues from Primary or Recurrent Breast Cancers.","authors":"Ilias P Nikas, Sojung Lim, Seock-Ah Im, Kyung-Hun Lee, Dae-Won Lee, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000533912","DOIUrl":"10.1159/000533912","url":null,"abstract":"<p><strong>Introduction: </strong>Immunohistochemistry (IHC) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarkers has prognostic and therapeutic value in breast cancer. This study aimed to compare the expression of ER, PR, and HER2 between paired malignant effusions and tissue samples of breast cancer.</p><p><strong>Methods: </strong>Our electronic archive was searched for all effusions diagnosed as breast carcinomas within a pre-defined period (January 2018-October 2021). Next, their cell blocks (CBs) were subjected to ER, PR, HER2 IHC, or in situ hybridization, in addition to EGFR IHC. The expression of hormone receptors (HRs) and HER2 was subsequently compared between tissue and effusion cytology samples derived from the same patients.</p><p><strong>Results: </strong>Only 2/76 (2.6%) of the breast cancer patients analyzed showed a malignant effusion at their initial presentation. ER, PR, and HER2 discordance rates between paired malignant effusions and tissue samples obtained at initial diagnosis were 24.3% (17/73), 40.8% (29/71), and 9.1% (6/66), respectively. The HR-/HER2- status was found more often at effusions compared to paired tissue biopsies obtained at initial diagnosis (30/70 vs. 17/70; p < 0.001). In addition, the HR-/HER2- status was significantly associated with an earlier development of a malignant effusion, when found at initial diagnosis (p < 0.001; log-rank test), first recurrence/metastasis (either solid or effusion) (p = 0.012; log-rank test), effusion samples (p = 0.007; log-rank test), and any tumor sample obtained (p = 0.009; log-rank test). Lastly, EGFR overexpression in the HR-/HER2- effusion samples was significantly associated with a shorter post-effusion survival (p = 0.019; log-rank test).</p><p><strong>Conclusion: </strong>Serous effusion cytology provides high-quality material for ancillary techniques, especially when CBs are prepared, reflecting cancer heterogeneity.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"169-179"},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41208322","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}