Journal of Pathology Clinical Research最新文献

{"title":"Validation of a whole slide image management system for metabolic-associated steatohepatitis for clinical trials","authors":"Hanna Pulaski,&nbsp;Shraddha S Mehta,&nbsp;Laryssa C Manigat,&nbsp;Stephanie Kaufman,&nbsp;Hypatia Hou,&nbsp;ILKe Nalbantoglu,&nbsp;Xuchen Zhang,&nbsp;Emily Curl,&nbsp;Ross Taliano,&nbsp;Tae Hun Kim,&nbsp;Michael Torbenson,&nbsp;Jonathan N Glickman,&nbsp;Murray B Resnick,&nbsp;Neel Patel,&nbsp;Cristin E Taylor,&nbsp;Pierre Bedossa,&nbsp;Michael C Montalto,&nbsp;Andrew H Beck,&nbsp;Katy E Wack","doi":"10.1002/2056-4538.12395","DOIUrl":"10.1002/2056-4538.12395","url":null,"abstract":"<p>The gold standard for enrollment and endpoint assessment in metabolic dysfunction-associated steatosis clinical trials is histologic assessment of a liver biopsy performed on glass slides. However, obtaining the evaluations from several expert pathologists on glass is challenging, as shipping the slides around the country or around the world is time-consuming and comes with the hazards of slide breakage. This study demonstrated that pathologic assessment of disease activity in steatohepatitis, performed using digital images on the AISight whole slide image management system, yields results that are comparable to those obtained using glass slides. The accuracy of scoring for steatohepatitis (nonalcoholic fatty liver disease activity score ≥4 with ≥1 for each feature and absence of atypical features suggestive of other liver disease) performed on the system was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement with a consensus “ground truth” score (defined as the median score of a panel of three pathologists’ glass slides). Each case was also read by three different pathologists, once on glass and once digitally with a minimum 2-week washout period between the modalities. It was demonstrated that the average agreement across three pathologists of digital scoring with ground truth was noninferior to the average agreement of glass scoring with ground truth [noninferiority margin: −0.05; difference: −0.001; 95% CI: (−0.027, 0.026); and <i>p</i> &lt; 0.0001]. For each pathologist, there was a similar average agreement of digital and glass reads with glass ground truth (pathologist A, 0.843 and 0.849; pathologist B, 0.633 and 0.605; and pathologist C, 0.755 and 0.780). Here, we demonstrate that the accuracy of digital reads for steatohepatitis using digital images is equivalent to glass reads in the context of a clinical trial for scoring using the Clinical Research Network scoring system.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges for pathologists in implementing clinical microbiome diagnostic testing","authors":"Yulia Gerasimova,&nbsp;Haroon Ali,&nbsp;Urooba Nadeem","doi":"10.1002/2056-4538.70002","DOIUrl":"https://doi.org/10.1002/2056-4538.70002","url":null,"abstract":"<p>Recent research has established that the microbiome plays potential roles in the pathogenesis of numerous chronic diseases, including carcinomas. This discovery has led to significant interest in clinical microbiome testing among physicians, translational investigators, and the lay public. As novel, inexpensive methodologies to interrogate the microbiota become available, research labs and commercial vendors have offered microbial assays. However, these tests still have not infiltrated the clinical laboratory space. Here, we provide an overview of the challenges of implementing microbiome testing in clinical pathology. We discuss challenges associated with preanalytical and analytic sample handling and collection that can influence results, choosing the appropriate testing methodology for the clinical context, establishing reference ranges, interpreting the data generated by testing and its value in making patient care decisions, regulation, and cost considerations of testing. Additionally, we suggest potential solutions for these problems to expedite the establishment of microbiome testing in the clinical laboratory.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expression of YAP1 and other transcription factors contributes to lineage plasticity in combined small cell lung carcinoma","authors":"Naoe Jimbo,&nbsp;Chiho Ohbayashi,&nbsp;Tomomi Fujii,&nbsp;Maiko Takeda,&nbsp;Suguru Mitsui,&nbsp;Yugo Tanaka,&nbsp;Tomoo Itoh,&nbsp;Yoshimasa Maniwa","doi":"10.1002/2056-4538.70001","DOIUrl":"https://doi.org/10.1002/2056-4538.70001","url":null,"abstract":"<p>Lineage plasticity in small cell lung carcinoma (SCLC) causes therapeutic difficulties. This study aimed to investigate the pathological findings of plasticity in SCLC, focusing on combined SCLC, and elucidate the involvement of YAP1 and other transcription factors. We analysed 100 surgically resected SCLCs through detailed morphological observations and immunohistochemistry for YAP1 and other transcription factors. Component-by-component next-generation sequencing (<i>n</i> = 15 pairs) and immunohistochemistry (<i>n</i> = 35 pairs) were performed on the combined SCLCs. Compared with pure SCLCs (<i>n</i> = 65), combined SCLCs (<i>n</i> = 35) showed a significantly larger size, higher expression of NEUROD1, and higher frequency of double-positive transcription factors (<i>p</i> = 0.0009, 0.04, and 0.019, respectively). Notably, 34% of the combined SCLCs showed morphological mosaic patterns with unclear boundaries between the SCLC and its partner. Combined SCLCs not only had unique histotypes as partners but also represented different lineage plasticity within the partner. NEUROD1-dominant combined SCLCs had a significantly higher proportion of adenocarcinomas as partners, whereas POU2F3-dominant combined SCLCs had a significantly higher proportion of squamous cell carcinomas as partners (<i>p</i> = 0.006 and <i>p</i> = 0.0006, respectively). YAP1 expression in SCLC components was found in 80% of combined SCLCs and 62% of pure SCLCs, often showing mosaic-like expression. Among the combined SCLCs with component-specific analysis, the identical <i>TP53</i> mutation was found in 10 pairs, and the identical <i>Rb1</i> abnormality was found in 2 pairs. On immunohistochemistry, the same abnormal p53 pattern was found in 34 pairs, and Rb1 loss was found in 24 pairs. In conclusion, combined SCLC shows a variety of pathological plasticity. Although combined SCLC is more plastic than pure SCLC, pure SCLC is also a phenotypically plastic tumour. The morphological mosaic pattern and YAP1 mosaic-like expression may represent ongoing lineage plasticity. This study also identified the relationship between transcription factors and partners in combined SCLC. Transcription factors may be involved in differentiating specific cell lineages beyond just ‘neuroendocrine’.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis","authors":"Sebastian Foersch,&nbsp;Maxime Schmitt,&nbsp;Anne-Sophie Litmeyer,&nbsp;Markus Tschurtschenthaler,&nbsp;Thomas Gress,&nbsp;Detlef K Bartsch,&nbsp;Nicole Pfarr,&nbsp;Katja Steiger,&nbsp;Carsten Denkert,&nbsp;Moritz Jesinghaus","doi":"10.1002/2056-4538.12394","DOIUrl":"10.1002/2056-4538.12394","url":null,"abstract":"<p>Antibody–drug conjugates (ADCs) directed to trophoblast cell surface antigen 2 (TROP2) have gained approval as a therapeutic option for advanced triple-negative breast cancer, and TROP2 expression has been linked to unfavourable outcomes in various malignancies. In colorectal carcinoma (CRC), there is still a lack of comprehensive studies on its expression frequency and its prognostic implications in relation to the main clinicopathological parameters. We examined the expression of TROP2 in a large cohort of 1,052 CRC cases and correlated our findings with histopathological and molecular parameters, tumour stage, and patient outcomes. TROP2 was heterogeneously expressed in 214/1,052 CRCs (20.3%), with only a fraction of strongly positive tumours. TROP2 expression significantly correlated with an invasive histological phenotype (e.g. increased tumour budding/aggressive histopathological subtypes), advanced tumour stage, microsatellite stable tumours, and p53 alterations. While TROP2 expression was prognostic in univariable analyses of the overall cohort (e.g. for disease-free survival, <i>p</i> &lt; 0.001), it exhibited distinct variations among important clinicopathological subgroups (e.g. right- versus left-sided CRC, microsatellite stable versus unstable CRC, Union for International Cancer Control [UICC] stages) and lost its significance in multivariable analyses that included stage and CRC histopathology. In summary, TROP2 is quite frequently expressed in CRC and associated with an aggressive histopathological phenotype and microsatellite stable tumours. Future clinical trials investigating anti-TROP2 ADCs should acknowledge the observed intratumoural heterogeneity, given that only a subset of TROP2-expressing CRC show strong positivity. The prognostic implications of TROP2 are complex and show substantial variations across crucial clinicopathological subgroups, thus indicating that TROP2 is a suboptimal parameter to predict patient prognosis.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma: collaboration between artificial intelligence and pathologists","authors":"Masahiro Adachi,&nbsp;Tetsuro Taki,&nbsp;Motohiro Kojima,&nbsp;Naoya Sakamoto,&nbsp;Kazuto Matsuura,&nbsp;Ryuichi Hayashi,&nbsp;Keiji Tabuchi,&nbsp;Shumpei Ishikawa,&nbsp;Genichiro Ishii,&nbsp;Shingo Sakashita","doi":"10.1002/2056-4538.12392","DOIUrl":"10.1002/2056-4538.12392","url":null,"abstract":"<p>Researchers have attempted to identify the factors involved in lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1-2, N0 (cT1-2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information. A dataset from 148 patients with cT1-2N0 tongue SCC was divided into training and test sets. The prediction models were constructed using AI-extracted information from whole slide images (WSIs), human-assessed clinicopathological information, and both combined. Weakly supervised learning and machine learning algorithms were used for WSIs and clinicopathological information, respectively. The combination model utilised both algorithms. Highly predictive patches from the model were analysed for histopathological features. In the test set, the areas under the receiver operating characteristic (ROC) curve for the model using WSI, clinicopathological information, and both combined were 0.826, 0.835, and 0.991, respectively. The highest area under the ROC curve was achieved with the model combining WSI and clinicopathological factors. Histopathological feature analysis showed that highly predicted patches extracted from recurrence cases exhibited significantly more tumour cells, inflammatory cells, and muscle content compared with non-recurrence cases. Moreover, patches with mixed inflammatory cells, tumour cells, and muscle were significantly more prevalent in recurrence versus non-recurrence cases. The model integrating AI-extracted histopathological and human-assessed clinicopathological information demonstrated high accuracy in predicting lymph node recurrence in patients with cT1-2N0 tongue SCC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEGFA gene variants are associated with breast cancer progression","authors":"Jessica Furriol,&nbsp;Elisabeth Wik,&nbsp;Sura Aziz,&nbsp;Cecilie Askeland,&nbsp;Gøril Knutsvik,&nbsp;Lars A Akslen","doi":"10.1002/2056-4538.12393","DOIUrl":"10.1002/2056-4538.12393","url":null,"abstract":"<p>Angiogenesis is recognized as a hallmark of cancer, and vascular endothelial growth factor (VEGF) is a key regulator of the angiogenic process and is related to cancer progression. Anti-VEGF therapy has been tried but with limited success and without useful stratification for angiogenesis markers. Further, the landscape of VEGF single nucleotide polymorphisms (SNPs) in breast cancer and their clinical relevance is not well studied, and their relation to tissue-based angiogenesis markers has not been explored. Here, we studied a selection of VEGFA SNPs in nontumor lymph nodes from a population-based breast cancer cohort (<i>n</i> = 544), and their relation to clinicopathologic variables, vascular tissue metrics, and breast cancer-specific survival. Two of the SNP candidates (rs833068GA genotype and rs25648CC genotype) showed associations with angiogenesis tissue markers, and the VEGFA rs833068GA genotype was associated with breast cancer-specific survival among ER-negative cases. We also found trends of association between the rs699947CA genotype and large tumor diameter and ER-negative tumors, and between the rs3025039CC genotype and large tumor diameter. Our findings indicate some associations between certain VEGF SNPs, in particular the rs833068GA genotype, and both vascular metrics and patient survival. These findings and their potential implications need to be validated by independent studies.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma","authors":"Xinyi Zhou,&nbsp;Haoxuan Ying,&nbsp;Yujie Sun,&nbsp;Wenda Zhang,&nbsp;Peng Luo,&nbsp;Shuhan Zhu,&nbsp;Jian Zhang","doi":"10.1002/2056-4538.12391","DOIUrl":"10.1002/2056-4538.12391","url":null,"abstract":"<p>Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic <i>BRCA1/2</i> mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03–333.76; <i>p</i> = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43–34.21; <i>p</i> = 0.016) compared with those in the HRD group. <i>In vitro</i> experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of PD-L1 expression with CD8+ T cells and oxidative stress-related molecules NRF2 and NQO1 in esophageal squamous cell carcinoma","authors":"Xin Zhang,&nbsp;Yanan Yang,&nbsp;Hongying Zhao,&nbsp;Zhongqiu Tian,&nbsp;Qing Cao,&nbsp;Yunlong Li,&nbsp;Yajuan Gu,&nbsp;Qinfei Song,&nbsp;Xiumei Hu,&nbsp;Mulan Jin,&nbsp;Xingran Jiang","doi":"10.1002/2056-4538.12390","DOIUrl":"10.1002/2056-4538.12390","url":null,"abstract":"<p>Oxidative stress and the immune microenvironment both contribute to the pathogenesis of esophageal squamous cell carcinoma (ESCC). However, their interrelationships remain poorly understood. We aimed to examine the status of key molecules involved in oxidative stress and the immune microenvironment, as well as their relationships with each other and with clinicopathological features and prognosis in ESCC. The expression of programmed death-ligand 1 (PD-L1), CD8, nuclear factor erythroid-2 related factor-2 (NRF2), and NAD(P)H quinone oxidoreductase 1 (NQO1) was detected using immunohistochemistry in tissue samples from 176 patients with ESCC. We employed both combined positive score (CPS) and tumor proportion score (TPS) to evaluate PD-L1 expression and found a positive correlation between CPS and TPS. Notably, PD-L1 expression, as assessed by either CPS or TPS, was positively correlated with both NRF2 nuclear score and NQO1 score in stage II–IV ESCC. We also observed a positive correlation between the density of CD8+ T cells and PD-L1 expression. Furthermore, high levels of PD-L1 CPS, but not TPS, were associated with advanced TNM stage and lymph node metastases. Moreover, both PD-L1 CPS and the nuclear expression of NRF2 were found to be predictive of shorter overall survival in stage II–IV ESCC. By using the Mandard-tumor regression grading (TRG) system to evaluate the pathological response of tumors to neoadjuvant chemotherapy (NACT), we found that the TRG-5 group had higher NRF2 nuclear score, PD-L1 CPS, and TPS in pre-NACT biopsy samples compared with the TRG-3 + 4 group. The NQO1 scores of post-NACT surgical specimens were significantly higher in the TRG-5 group than in the TRG 3 + 4 group. In conclusion, the expression of PD-L1 is associated with aberrant NRF2 signaling pathway, advanced TNM stage, lymph node metastases, and unfavorable prognosis. The dysregulation of PD-L1 and aberrant activation of the NRF2 signaling pathway are implicated in resistance to NACT. Our findings shed light on the complex interrelationships between oxidative stress and the immune microenvironment in ESCC, which may have implications for personalized therapies and improved patient outcomes.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.12390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesonephric-type adenocarcinomas of the ovary: prevalence, diagnostic reproducibility, outcome, and value of PAX2","authors":"Martin Köbel,&nbsp;Eun Young Kang,&nbsp;Sandra Lee,&nbsp;Travis Ogilvie,&nbsp;Tatjana Terzic,&nbsp;Linyuan Wang,&nbsp;Nicholas JP Wiebe,&nbsp;Zainab Al-Shamma,&nbsp;Linda S Cook,&nbsp;Gregg S Nelson,&nbsp;Colin JR Stewart,&nbsp;Andreas von Deimling,&nbsp;Felix KF Kommoss,&nbsp;Cheng-Han Lee","doi":"10.1002/2056-4538.12389","DOIUrl":"10.1002/2056-4538.12389","url":null,"abstract":"<p>Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (<i>κ</i> = 0.376–0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62–5.85; <i>p</i> &lt; 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma","authors":"Yuta Kaneko,&nbsp;Tsukasa Masuda,&nbsp;Kimiharu Takamatsu,&nbsp;Shuji Mikami,&nbsp;Kohei Nakamura,&nbsp;Hiroshi Nishihara,&nbsp;Ryuichi Mizuno,&nbsp;Nobuyuki Tanaka,&nbsp;Mototsugu Oya","doi":"10.1002/2056-4538.12388","DOIUrl":"10.1002/2056-4538.12388","url":null,"abstract":"<p>Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two-dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three-dimensional light-sheet microscopy. Here, we used the diagnosing immunolabeled paraffin-embedded cleared organs pipeline for tissue clearing, immunolabeling, and three-dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE-1, which targets lymphatic vessels, were examined by calculating three-dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin-fixed paraffin-embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three-dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K-mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High-end tissue clearing techniques and volumetric immunohistochemistry enable three-dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"10 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}