Fahad Sheikh, Susan Fineberg, Javier Laurini, Sonali Lanjewar
{"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}
Kritika Krishnamurthy, Xing Li, Jui Choudhuri, Yang Shi, Yanhua Wang
{"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}
Nuha Shaker, Jon Davison, Joshua Derby, Ibrahim Abukhiran, Akila Mansour, Matthew Holtzman, Haroon Choudry, Reetesh K Pai
{"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}
Justin T Kelley, Haley M Amoth, Nicolas Lopez-Hisijos, Steven Hrycaj, Riccardo Valdez, Douglas Rottmann
{"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":"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}
{"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":"Overexpression of MAGE-A2 is Related to the Malignant Degree and Progression of Disease in Patients With Clear Cell Renal Cell Carcinoma.","authors":"Monireh Mohsenzadegan, Fahimeh Fattahi, Elham Kalantari, Maryam Abolhasani, Zahra Madjd, Leili Saeednejad Zanjani","doi":"10.1097/PAI.0000000000001243","DOIUrl":"10.1097/PAI.0000000000001243","url":null,"abstract":"<p><p>Melanoma antigen gene-A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in a variety of malignancies. However, the expression of MAGE-A2 for clinical values in the pathophysiology of renal cell carcinoma (RCC) is unknown. For the first time, the present study was conducted to examine the expression and prognostic significance of MAGE-A2 expression in clear cell RCC (ccRCC). MAGE-A2 expression was assayed in 162 well-defined ccRCC samples using immunohistochemistry staining on tissue microarrays. The association between MAGE-A2 expression and clinic-pathologic features as well as survival outcomes were then performed. A significant and positive correlation was found between cytoplasmic expression of MAGE-A2 with tumor size ( P =0.008), nucleolar grade ( P =0.001), tumor stage ( P =0.001), microvascular invasion ( P =0.001), invasion to renal pelvis ( P =0.032), renal sinus fat ( P =0.004), and Gerota's fascia ( P =0.028) as well as histologic tumor necrosis ( P <0.0001). Increased expression of MAGE-A2 was observed to be associated with shorter progression-free survival (PFS) compared with patients with low expression of MAGE-A2 ( P =0.032). Multivariate analysis revealed that tumor size and nucleolar grade are independent predictors of the PFS ( P =0.054, P =0.032, respectively). Our results indicated that increased cytoplasmic expression of MAGE-A2 is associated with the malignant degree and progression of ccRCC. This data improved the significance of MAGE-A2 expression and will potentially allow using MAGE-A2 for the prognosis of the disease and immunotherapy in patients with ccRCC.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"78-90"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972956","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":"Immunohistochemical Investigation of the Proliferative Activity of Odontogenic Cysts and Tumors.","authors":"Manal A Alsheddi","doi":"10.1097/PAI.0000000000001240","DOIUrl":"10.1097/PAI.0000000000001240","url":null,"abstract":"<p><p>Odontogenic cysts and tumors exhibit a broad spectrum of biological characteristics. Despite recent advances in understanding the complex nature of these lesions, relatively less is known about the molecular markers involved in key pathogenic steps, such as proliferation and differentiation. This study aimed to elucidate the expression patterns of p63 and Ki-67 in odontogenic lesions, which may influence the management strategies. Forty-two specimens from the archives of the Histopathology Laboratory, including conventional ameloblastoma, unicystic ameloblastoma, odontogenic keratocysts, dentigerous cysts, and orthokeratinized cysts, were analyzed. Immunohistochemistry was performed using antibodies against p63 and Ki-67. Digital image analysis was performed using an Aperio slide scanner and QuPath software. Ki-67 levels were higher in odontogenic keratocysts (OKCs), indicating a greater proliferative index, whereas p63 expression was significantly higher in ameloblastomas and OKCs than in dentigerous cysts. No significant difference in p63 expression was observed between the ameloblastoma types. The results revealed variable Ki-67 and p63 expression in the odontogenic epithelium of the investigated odontogenic lesions, suggesting their potential roles in the biological behavior and aggressiveness of these lesions. This study highlights the differential expression pattern of Ki-67 and p63 and their potential involvement in the pathogenesis of these rare lesions. In addition, the study reinforces the need for more comprehensive molecular analyses using a larger sample. The results contribute to a better understanding of the complex nature of these lesions, which may facilitate improving the management options of odontogenic cysts and tumors.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"111-116"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688868","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}
Joan Lop Gros, Pablo Santiago Díaz, Mónica Larrubia Loring, Maria E Patriarca, Belen Lloveras, Mar Iglesias
{"title":"Claudin 18.2 Immunohistochemistry Expression in Gastric Cancer: A Systematic Review.","authors":"Joan Lop Gros, Pablo Santiago Díaz, Mónica Larrubia Loring, Maria E Patriarca, Belen Lloveras, Mar Iglesias","doi":"10.1097/PAI.0000000000001248","DOIUrl":"10.1097/PAI.0000000000001248","url":null,"abstract":"<p><p>Claudin 18.2 is a transmembrane protein, part of the tight-junction complex, selectively expressed in gastric epithelium. It is showing promising results as a target in advanced gastric cancer in phase 3 clinical trials using a monoclonal antibody against claudin 18.2. A systematic review on expression of claudin 18.2 in gastric cancer was performed using the PubMed database. The following search expression was used: (\"Stomach Neoplasms\" [Mesh]) AND ((\"claudin-18[TIAB]\") OR (\"CLDN18[TIAB]\")). A total of n=99 articles were retrieved. Of those, 17 preclinical studies about claudin 18.2 expression by immunohistochemistry were selected. The results of those studies showed great variability in the criteria used for defining the thresholds for positivity of the stain. The proportion of claudin 18.2 positive cases varied between 24% and 83%. In works using a positivity threshold set at >40% or >70% of cells with membranous/cytoplasmic staining at 2+/3+ intensity, the average rate of positive cases was 50% or 30%, respectively (similar with clones 43-14A and EPR19202). Positivity of claudin 18.2 was associated with advanced stage, diffuse phenotype and PD-L1 and EBV positivity in some of the studies. Variability in criteria used to define claudin 18.2 positivity, as well as methodological differences, could explain the variation in the proportion of positive cases described, as well as the inconsistency of the association with clinical, molecular, and survival variables. The upcoming anticlaudin 18.2 therapy in advanced gastric cancer should prompt pathology laboratories to adjust their staining protocols and evaluation criteria in their series of patients, to further establish the association of claudin expression with clinical and molecular variables.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"61-69"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081725","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}
Cameron Beech, Diane M Wilcock, Kristina H Moore, Leslie Rowe, Jonathan Mahlow, Jolanta Jedrzkiewicz, Allison S Cleary, Lesley Lomo, Ana L Ruano, Maarika Gering, Derek Bradshaw, Meghan Maughan, Phuong Tran, Richard Davis, Kajsa Affolter, Daniel J Albertson, Parisa Adelhardt, JongTaek Kim, Joshua F Coleman, Georgios Deftereos, Evin H Gulbahce, Deepika Sirohi
{"title":"Changes in HER2 Amplification Status for Breast Cancer Patients After Immunohistochemistry Directed In Situ Hybridization.","authors":"Cameron Beech, Diane M Wilcock, Kristina H Moore, Leslie Rowe, Jonathan Mahlow, Jolanta Jedrzkiewicz, Allison S Cleary, Lesley Lomo, Ana L Ruano, Maarika Gering, Derek Bradshaw, Meghan Maughan, Phuong Tran, Richard Davis, Kajsa Affolter, Daniel J Albertson, Parisa Adelhardt, JongTaek Kim, Joshua F Coleman, Georgios Deftereos, Evin H Gulbahce, Deepika Sirohi","doi":"10.1097/PAI.0000000000001247","DOIUrl":"10.1097/PAI.0000000000001247","url":null,"abstract":"<p><p>The 2018 ASCO/CAP guidelines for HER2 testing for breast cancer implemented the addition of immunohistochemistry (IHC) directed in situ hybridization (ISH) recount to resolve equivocal results. The implementation of an additional 2+ IHC-directed ISH recount adds additional complexity to the testing workflow for an unclear impact on HER2 results. A retrospective review of all equivocal ISH cases (groups 2, 3, and 4) that underwent 2+ IHC-directed ISH, since the 2018 guidelines, which were finalized as either amplified or not amplified, was performed. HER2 group number and final HER2 amplification status frequently changed after IHC guided ISH assessment, which was due to significant changes in HER2/CEP17 ratio and average HER2 signal number per cell. Equivocal groups 2, 3, and 4 samples with a result of HER2 amplified after 2+ IHC-directed ISH counts were closer to the threshold for amplification on the original ISH count, yet their counts also increased significantly after IHC-directed count in comparison to those samples, which were not amplified. Groups 2 and 4 ISH counts significantly increased after IHC directed ISH for HER2/CEP17 ratio and HER2 signal number per cell. This study represents the most extensive examination of efforts to resolve equivocal HER2 ISH results, highlighting a significant shift in therapeutic options after IHC-guided ISH for a subset of breast cancer patients.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"91-102"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048421","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}