Applied Immunohistochemistry & Molecular Morphology最新文献

{"title":"Expression of EZH2 and Fatty Acid Synthase in Breast Tissues From Healthy Women With Breast Cancer Risk Factors.","authors":"Katelyn Zebrowski, Kaleb June, Dafydd Thomas, Zora Djuric, Tarah Ballinger, Celina G Kleer","doi":"10.1097/PAI.0000000000001250","DOIUrl":"10.1097/PAI.0000000000001250","url":null,"abstract":"<p><p>Tissue-based biomarkers that identify women with increased breast cancer risk are needed for cancer prevention. Enhancer of zeste 2 (EZH2) and fatty acid synthase (FASN) are associated with breast cancer aggressiveness, but their expression in normal breast tissues and association with breast cancer risk factors are unclear. Further, there is a need to characterize healthy breast tissue cohorts for unbiased biomarker evaluation. In this study, we employed the Susan G. Komen healthy volunteer tissue bank to evaluate EZH2 and FASN expression and their relationship to breast cancer risk factors. Normal breast core biopsies from 40 healthy donors with low or high Gail scores (<11 or >20, respectively) and normal or obese body mass index (BMI, <25 kg/m 2 or >30 kg/m 2 , respectively) were stained for H&E, EZH2, and FASN and scored independently and blindly using the Allred method. We analyzed the associations between EZH2 and FASN with Gail score, BMI, menopausal status, hormone replacement therapy (HRT), and family history of breast cancer. None of the donors had BRCA1/2 mutations or developed breast cancer after 5 to 9 years. We found that premenopausal women had significantly higher expression of FASN and that EZH2 was higher with increasing Gail risk scores, compared with postmenopausal women. In postmenopausal women, increased EZH2 expression was associated with >5 years of HRT compared with <1 year or no HRT. No associations were found with BMI. This study provides validation of a healthy breast tissue cohort and initial characterization of EZH2 and FASN and their associations with breast cancer risk factors.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781484","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":"Classifying Pulmonary and Urinary High-grade Neuroendocrine Carcinoma by CK7 Immunohistochemistry: Erratum.","authors":"","doi":"10.1097/PAI.0000000000001255","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001255","url":null,"abstract":"","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732691","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":"Toward Accurate Deep Learning-Based Prediction of Ki67, ER, PR, and HER2 Status From H&E-Stained Breast Cancer Images.","authors":"Amir Akbarnejad, Nilanjan Ray, Penny J Barnes, Gilbert Bigras","doi":"10.1097/PAI.0000000000001258","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001258","url":null,"abstract":"<p><p>Despite improvements in machine learning algorithms applied to digital pathology, only moderate accuracy, to predict molecular information from histology alone, has been achieved so far. One of the obstacles is the lack of large data sets to properly train machine learning models. We therefore built a data set of 185,538 breast cancer (BC) including hematoxylin and eosin (H&E) and associated immunohistochemistry (IHC) images of the proliferative marker Ki67, estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). Optimal registration of H&E and IHC pairs was achieved. Ki67, ER, and PR IHC labels, to be predicted, were extracted from IHC assays using image analysis. These labels were ordinaly classified with incremental thresholds (cumulative logit models with balanced and partial proportional odds). HER2 label was determined as follows: positive if tumor IHC 3+ pattern is identified and otherwise negative. Cases with IHC equivocal score (2+) were excluded. A vision transformer (ViT)-based pipeline, trained with this data set, achieved prediction performance of 90% in terms of area under the curve (AUC) of the receiver operating characteristic (ROC) curves. ViT outperformed the weakly supervised clustering-constrained attention multiple instance learning (CLAM) which was developed to automatically identify subregions of high diagnostic value in whole slide. As a first step to \"explain\" artificial intelligence (AI), we evaluated the ability of both classifiers to localize these high diagnostic value subregions by inspecting their respective \"attention\" heat-maps. Despite high ViT AUC-ROC results, heat-maps do not obviously match areas of high diagnostic value subregions; it might however provide direction for future work to improve AI attention within whole slide images. Our proposed data set is publicly available.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721924","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":"Genetic and Epigenetic Changes in Melanoma Progression: A TCGA-based Study.","authors":"Yasemin Cakir, Banu Lebe, M Hasan Toper, Sulen Sarioglu","doi":"10.1097/PAI.0000000000001257","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001257","url":null,"abstract":"<p><p>We aimed to investigate molecular mechanisms affecting melanoma progression by comparing genetic/epigenetic features between melanomas of different Breslow thickness and stage using TCGA (The Cancer Genome Atlas) data. The TCGA, Firehose Legacy, melanoma data set was utilized on the cBioPortal website. The cases were compared in terms of mRNA expression and DNA methylation. Gene Ontology (GO) and KEGG pathways enrichment analysis were performed using the online WebGestalt tool. STRING and Cytoscape software were used to construct a protein-protein interaction network and identify hub genes. P and q<0.05, FDR< 0.05 were considered statistically significant. 1001 differentially expressed genes were identified between thin (≤1 mm) and thick (>1 mm) melanomas. Pathway analyses revealed that genes enriched in thin melanomas were associated with adaptive immune response, T-cell activation, immune response regulation, leukocyte, and cytokine-related pathways, whereas genes enriched in thick melanomas were related to epidermis development. Ten hub genes were identified (CD4, IFNG, PTPRC, CD8A, CTLA4, CD69, ICOS, CD27, CD28, CD19). All of these genes are involved in crucial immunological processes. Understanding the complex changes in melanoma progression is essential for accurate diagnosis and prediction of prognosis. Our results may shed light on subsequent studies to identify the steps in melanoma progression.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701872","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":"Loss of Cytokeratin 7 (CK7) Expression Can be Seen in Significant Proportion of Solid Papillary Carcinoma of Breast and Associated Invasive Component.","authors":"Fahad Sheikh, Susan Fineberg, Javier Laurini, Sonali Lanjewar","doi":"10.1097/PAI.0000000000001256","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001256","url":null,"abstract":"<p><strong>Abstract: </strong>Cytokeratin 7 (CK7) is a marker of epithelial differentiation and is positive in >90% of breast carcinomas. In the right clinical setting, coexpression of CK7 and GATA3 is considered as strong evidence of breast origin, which can be further confirmed by positive expression of estrogen and progesterone receptors. Pathologists use CK7 in the breast to confirm epithelial differentiation and highlight foci of invasion, and outside the breast it is often used as a marker to support breast origin of metastatic tumors. Few studies have reported loss of CK7 in invasive breast carcinoma, however, association of CK7 loss with any histopathologic subtype has not been well documented in the literature. We stained a series of solid papillary carcinoma of the breast (SPC) and associated invasive ductal carcinoma (IDC) with CK7 to document that CK7 loss can occur in both SPC and associated IDC. Archived breast tumor tissue specimens with a diagnosis of SPC with IDC were identified from our Department of Pathology database from January 2019 to January 2023. Blocks with tumors were initially evaluated on Hematoxylin and Eosin (H&E) slides, and subsequently with CK7, synaptophysin, and chromogranin immunostains. The results of these immunohistochemical markers were tabulated in an Excel sheet. Expression of CK7 was entered as negative, marked loss of CK7 (weak positive staining in <1% of tumor), and positive (diffuse expression >1% to 100% of tumor cells). Out of 26 tumors of SPC, 15 showed negative to a marked loss of expression for CK7 in both in-situ and invasive components (57.7%), while 11 were diffusely positive (42.3%). Neuroendocrine differentiation was present in 57.7% of tumors of which 60% were CK7 negative. However, there was no significant association between neuroendocrine differentiation in SPC and associated IDC with CK7 loss (P=1). In addition, histologic parameters, biomarkers expression, Ki-67 expression, and clinical follow-up were studied in detail.</p><p><strong>Conclusion: </strong>A significant proportion of solid papillary carcinoma of the breast and the associated invasive component can show loss of CK7.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659359","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 Impact of Type, Dose, and Duration of Prebiopsy Corticosteroids Use on Histomorphology and Immunohistochemical Stains in B-Cell Lymphoma: A Case-Control Study to Highlight the \"Atypical\" Cytoplasmic and Extra-Cellular Granular Staining Pattern of CD20.","authors":"Kritika Krishnamurthy, Xing Li, Jui Choudhuri, Yang Shi, Yanhua Wang","doi":"10.1097/PAI.0000000000001252","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001252","url":null,"abstract":"<p><p>Large/aggressive B-cell lymphomas are diverse both in terms of clinical presentations and treatment response. Diagnostic pathologic evaluation typically begins with a CD20/CD3 immunohistochemical panel. Prebiopsy steroid treatment has been reported to delay diagnosis and subsequent treatment due to altering histomorphology and immunohistochemical staining patterns. This study investigates the impact of prebiopsy steroid use on morphology and immunohistochemical staining patterns in large B cell lymphoma and/or mature B cell lymphomas with high Ki67 expression. Fourteen cases of B cell lymphoma treated with prebiopsy steroids and 13 cases of treatment-naive large B cell lymphoma and/or mature B cell lymphomas with high Ki67 expression were included in this study. Clinicopathological parameters, including type, dose, and route of steroid administration, were documented. Histopathologic slides from both groups were examined to assess morphology and immunohistochemical staining patterns. Morphologically significant effects attributable to steroid administration included significant histiocytic infiltrate and lack of diffuse pattern of infiltration of the lymphoma cells. The CD20 staining pattern, characterized by cytoplasmic/granular distribution and extracellular spillage, showed a statistically significant increase in the steroid group compared with the control group (P=0.011). This alteration was more prevalent among patients treated with intravenous dexamethasone, high-dose corticosteroids over a short term, and with shorter dosing intervals. Prebiopsy corticosteroid administration induces changes in histomorphology and immunohistochemical staining patterns, particularly affecting CD20, thereby posing diagnostic challenges. The extent of these effects varies depending on the type, route, dosage, and duration of steroid administration.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574458","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":"Smooth Muscle Myosin Heavy Chain Expression in Nodal and Extranodal Follicular Dendritic Cell Sarcoma.","authors":"Justin T Kelley, Haley M Amoth, Nicolas Lopez-Hisijos, Steven Hrycaj, Riccardo Valdez, Douglas Rottmann","doi":"10.1097/PAI.0000000000001241","DOIUrl":"10.1097/PAI.0000000000001241","url":null,"abstract":"<p><p>Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm requiring a high index of suspicion, especially on small biopsies. Smooth muscle myosin heavy chain (SMMHC) is a common immunohistochemical (IHC) stain that has been reported to mark normal nodal follicular dendritic cells (FDCs). We hypothesize that SMMHC can be a sensitive marker for FDCS and aim to compare its performance with established markers of FDCS. The archive of a large academic center was searched for cases of FDCS. Clinical features, including age, sex, and site at diagnosis, were reviewed. A hematoxylin and eosin-stained slide was evaluated to assess for morphology and presence of hyaline vascular Castleman disease. The established FDC markers CD21, CD23, fascin, clusterin, and D2-40 were reviewed and compared with SMMHC for all cases. The staining pattern was classified as positive (strong or weak) or negative. Seven unique cases of nodal and extranodal FDCS were collected. SMMHC was positive in most cases (n=5) and performed similarly to established FDC markers, including clusterin, CD21, and CD23 (n=7 each), and fascin and D2-40 (n=4 each). SMMHC was also negative in all 14 examined cases among 5 common differential diagnoses. We demonstrate that the common IHC marker SMMHC has high specificity and similar sensitivity as established FDC markers in nodal and extranodal FDCS, and is useful in the evaluation of common neoplastic mimics.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"103-110"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957104","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":"TP53 Alterations Are an Independent Adverse Prognostic Indicator in Pseudomyxoma Peritonei of Appendiceal Origin Following Cytoreductive Surgery and Intraperitoneal Chemotherapy.","authors":"Nuha Shaker, Jon Davison, Joshua Derby, Ibrahim Abukhiran, Akila Mansour, Matthew Holtzman, Haroon Choudry, Reetesh K Pai","doi":"10.1097/PAI.0000000000001245","DOIUrl":"10.1097/PAI.0000000000001245","url":null,"abstract":"<p><p>Histologic grade is a key predictor for pseudomyxoma peritonei (PMP) of appendiceal origin that is used to guide clinical management. However, some tumors demonstrate disease behavior that deviates from their histologic grade. A recent study suggested that TP53, GNAS , and RAS mutation analysis could stratify tumors into distinct molecular groups with different prognosis. We investigated molecular alterations in 114 patients with PMP of appendiceal origin who were uniformly treated with cytoreductive surgery with intraperitoneal chemotherapy (CRS+IPCT). Tumors were separated into 4 groups based on their predominant genomic alteration: RAS -mut, GNAS -mut, TP53 -mut, and triple-negative ( RAS/GNAS/TP53 -wildtype). The results were correlated with World Health Organization (WHO) grade, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS) from the time of CRS+IPCT using multivariate Cox proportional hazard analysis. Fifty percent of TP53 -mut were WHO grade 3 compared with 38% triple-negative, 10% RAS -mut, and 7% GNAS -mut tumors ( P <0.001). The TP53 -mut group exhibited a significantly reduced OS compared with other groups ( P <0.001). No significant OS difference was identified between RAS -mut, GNAS -mut, and triple-negative groups ( P >0.05). In grade 3 PMP, TP53 -mut was significantly associated with reduced OS ( P =0.002). In the multivariate analysis for OS after CRS+IPCT, TP53 -mut [hazard ratio (HR) 3.23, P =0.004] and WHO grade (grade 2 HR 2.73, P =0.03 and grade 3 HR 5.67, P <0.001) were the only independent predictors of survival. Our results suggest that, in addition to tumor grade, TP53 status may help to provide a more patient-centered approach in guiding therapy in PMP.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"70-77"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985063","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 Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis.","authors":"Yasemin Cakir, Banu Lebe","doi":"10.1097/PAI.0000000000001242","DOIUrl":"10.1097/PAI.0000000000001242","url":null,"abstract":"<p><p>PRAME is a cancer testis antigen whose expression is limited in normal tissues but is increased in cancers. Although there are studies revealing its oncogenic and immunogenic role, the relationship between PRAME expression and immunity in melanomas is not very clear. We aimed to reveal the relationship between PRAME expression and clinicopathologic parameters, immunologic markers, survival in melanomas. PRAME alteration data in TCGA SKCM data set was obtained from cBioPortal. Analyzes regarding clinicopathologic parameters were performed through cBioPortal and UALCAN, survival-related analyzes were performed through cBioPortal, GEPIA2. The correlation analyzes between PRAME expression and immune cell infiltration, immunity-related genes were performed in TIMER2.0, TISIDB, GEPIA2. PRAME protein-protein interaction network was constructed in STRING. The correlated genes with PRAME were listed in LinkedOmics, gene set enrichment and pathway analyses were performed through LinkInterpreter. In cases with low PRAME expression, there was a higher frequency of metastasis and p53 mutation, a more advanced tumor stage and a lower nodal stage. Strong relationship between PRAME expression and immune cell infiltration. A negative correlation was detected between expression of PRAME and many immunomodulatory genes ( P <0.05). Positively correlated genes with PRAME expression were involved in metabolic pathways; negatively correlated genes were involved in pathways related to cell differentiation, immunologic processes. No significant relationship was found between PRAME expression and survival ( P >0.05). Our findings reveal a strong interaction between PRAME expression and tumorigenicity, the immune system and shed light on further clinical studies including PRAME -targeted studies.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"117-130"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957110","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":"From Microscopes to Milestones: Leveraging Social Media to Transform Pathology Scholarship.","authors":"Katrina Collins","doi":"10.1097/PAI.0000000000001244","DOIUrl":"10.1097/PAI.0000000000001244","url":null,"abstract":"","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"59-60"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985061","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}