Applied immunohistochemistry & molecular morphology : AIMM最新文献

{"title":"A Study on Differential Proteomics in Differentiated Gastric Adenocarcinoma With Low-grade Atypia Based on Paraffin-embedded Tissues.","authors":"Xuan-Tao Yang, Yu Zhang, Yue-Jiao Ding, Ying-Hong Zhang, Yan-Qiong Xu, Qing-Qing Zheng, Peng-Jie Liu, Ming Tang","doi":"10.1097/PAI.0000000000001298","DOIUrl":"10.1097/PAI.0000000000001298","url":null,"abstract":"<p><p>In this study, we analyzed and characterized differentially expressed proteins in differentiated gastric adenocarcinoma with low-grade atypia for screening potential protein markers. We collected gastric tissue specimens from 90 patients treated at the Pathology Department of the First People's Hospital of Yunnan Province, China, between January 2019 and December 2022. These specimens had been fixed in 10% neutral-buffered formalin and embedded in paraffin. We classified these samples into 3 groups: the control group (normal gastric mucosa), the low-grade atypia group (differentiated gastric adenocarcinoma with low-grade atypia), and the high-grade atypia group (differentiated gastric adenocarcinoma with high-grade atypia), consisting of 30 cases in each group. We analyzed differential proteomes with the data-independent acquisition-mass spectrometry (DIA-MS) methodology and selected 4 differentially expressed proteins that were subjected to immunohistochemistry (IHC) staining for validation. A total of 4406 proteins were identified, among which 598 and 357 proteins were statistically different in the low-grade atypia group as compared with the control group and the high-grade atypia group, respectively. IHC staining showed that the expression of FHL3, CSRP2, and FCGR3A was significantly higher in the low-grade atypia group than in the control group ( P <0.05) and significantly higher in the high-grade atypia group than in the low-grade atypia group ( P <0.05). FHL2 expression was negative to weakly positive in the control and low-grade atypia groups and not significantly different between the 2 groups, whereas FHL2 expression in the high-grade atypia group was significantly higher than in the control and low-grade atypia groups ( P <0.05). Proteomic analysis is helpful for discovering new protein markers. Using a combination of FHL3, CSRP2, and FCGR3A can increase the accuracy of the pathologic diagnosis of differentiated gastric adenocarcinoma with low-grade atypia.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"320-329"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological Significance of Leucine-rich Repeat-containing 15 in Distal Extrahepatic Bile Duct Carcinoma.","authors":"Jihyun Chun, Deok-Beom Jung, Jinho Shin, Hyehyun Jeong, Changhoon Yoo, Seung-Jae Myung, Seung-Mo Hong","doi":"10.1097/PAI.0000000000001341","DOIUrl":"10.1097/PAI.0000000000001341","url":null,"abstract":"<p><p>Leucine-rich repeat-containing 15 (LRRC15) is a membrane protein whose overexpression has been linked to poorer survival outcomes in various malignant neoplasms. However, its role in distal extrahepatic bile duct carcinoma (DBDC) remains unclear. LRRC15 protein expression in tumor cells and stroma was evaluated with 196 surgically resected DBDCs, and compared with clinicopathological variables, including patients' overall survival (OS) and recurrence-free survival (RFS). LRRC15 protein expression was identified in stroma of 21 DBDCs (11%) and tumor cells in 67 cases (34%). On the basis of the combined expression patterns of LRRC15, DBDCs were classified into 4 groups: LRRC15 cancer+/stroma- (25%), cancer-/stroma+ (2%), cancer+/stroma+ (9%), and cancer-/stroma- (64%). The stromal LRRC15+ group exhibited more frequent pancreatic invasion compared with the stromal LRRC15- group ( P =0.004*). The LRRC15 cancer+/stroma+ group showed the most frequent pancreas invasion ( P =0.016*). The patients with stromal LRRC15+ group had significantly worse OS (5-year survival rate, 15.4% vs. 31.6%; P =0.013*) and RFS (19.1% vs. 38.9%; P =0.005*) compared with those in the stromal LRRC15- DBDCs. Stromal LRRC15 expression was significantly associated with poor prognosis and showed a strong trend toward being an independent prognostic factor for both OS ( P =0.051) and RFS ( P =0.061). Patients with DBDCs in the LRRC15 cancer+/stroma+ group had the worst RFS ( P =0.010*) and OS ( P =0.008*) by univariate analysis. LRRC15 overexpression was observed in a subset of DBDCs and was associated with pancreatic invasion and worse OS and RFS. Consequently, LRRC15 expression can be used as an indicator of poor survival in patients with DBDCs, particularly when both cancer cells and stromal expression are present.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"304-313"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tissue Processing Technique for Improving Slide Preparation Quality of ESD Specimens.","authors":"Shanshan Huang, Xiaodan Fu, Yu Zhang, Ping Wu, Yupeng Chen, Mi Wang, Huinan Lu, Sheng Zhang, Guoping Li","doi":"10.1097/PAI.0000000000001323","DOIUrl":"10.1097/PAI.0000000000001323","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of endoscopic submucosal dissection (ESD) procedures and subsequent treatment is predominantly reliant on precise pathologic evaluation, intricately linked to specimen sampling and paraffin sectioning. Despite established guidelines in China for ESD specimen processing, the postsampling process remains intricate and error-prone. This study investigates the impact of various placement and labeling methods following ESD sampling on the quality of paraffin slides and the precision of pathologic diagnoses, with the ultimate goal of identifying the most effective approach.</p><p><strong>Methods: </strong>We selected 45 ESD specimens and used 3 distinct postsampling placement and labeling methods: the conventional method, the sponge sandwich placement method, and the sponge interstitial vertical embedding method. Routine HE, IHC, and specific staining were performed to evaluate the effect.</p><p><strong>Results: </strong>Our findings demonstrated that both the sponge sandwich placement and sponge interstitial vertical embedding methods resulted in superior HE preparation quality compared with the conventional method, with no discernible difference in HE preparation quality between the sponge sandwich and sponge interstitial vertical embedding methods. It was also verified by IHC and special staining. Nevertheless, the sponge sandwich placement method resulted in irregular marking of the dehydration box, making it challenging for technicians to determine the embedding direction of the specimens without a bulge or without remembering the embedding phenomenon. In contrast, the sponge interstitial vertical placement and labeling embedding method obviates the need to recognize the embedding direction of the specimen and tissues to be embedded; embedding is guided solely by the morphology and direction of the doctor-placed sponge.</p><p><strong>Conclusions: </strong>Based on our laboratory experience, we advocate for the sponge interstitial vertical embedding method.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"347-353"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumorigenesis of Hepatocellular Carcinoma Related to Metabolic Disorders With a Focus on the Hippo Pathway.","authors":"Haruto Nishida, Keiko Matsuura, Tsutomu Daa","doi":"10.1097/PAI.0000000000001338","DOIUrl":"10.1097/PAI.0000000000001338","url":null,"abstract":"<p><p>The Hippo pathway has been implicated in the tumorigenesis of hepatocellular carcinoma (HCC). We aimed to determine the expression of Hippo pathway-related proteins in HCC using immunohistochemical staining and compare the data among patients with different underlying clinical background diseases. We collected 40 resected HCC formalin-fixed paraffin-embedded samples and categorized them into 4 groups according to pre-existing conditions [17 samples of alcohol consumption (HCC-A) and 6, 8, and 9 samples with hepatitis B virus infection (HCC-B), hepatitis C virus infection (HCC-C), and metabolic diseases (HCC-M), respectively]. Using immunohistochemistry, we investigated the Hippo pathway-related proteins YAP1, CADM1, and SOX9. Hypertension was the most common disease (72.5%) among patients with HCC, followed by diabetes mellitus (47.5%). Regarding the background liver disease, significant findings of steatohepatitis (SH) were observed in the HCC-A (35.3%) and HCC-M (88.9%) groups compared with those in the HCC-B (16.7%) and HCC-C (0%) groups. A significant finding of metabolic dysfunction-associated SH (MASH) was also observed in the HCC-M group (88.9%), and liver cirrhosis was predominantly observed in the HCC-C group (100%). Twenty-seven patients had Hippo-inactive status, and 13 patients had active status. SH was more predominant in the HCC-M group with Hippo inactivity (100%) than in the HCC-A group (50.0%). The average tumor size was significantly larger in the Hippo-inactive group than in the Hippo-active group. Hippo pathway-associated proteins could serve as potential therapeutic targets for MASH and MASH-related HCC if the Hippo pathway is inactivated.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"314-319"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRAME Expression in Merkel Cell Carcinoma: Correlation With MCPyV Status, PD-L1, and Tumor-Infiltrating Lymphocytes in a Multicenter Cohort.","authors":"Erdem Comut, Betul Ogut, Arbil Acikalin, Ozlem Erdem, Nese Calli Demirkan","doi":"10.1097/PAI.0000000000001352","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001352","url":null,"abstract":"<p><p>Preferentially expressed antigen in melanoma (PRAME) expression has been described in Merkel cell carcinoma (MCC), but its clinicopathologic and biological significance remains incompletely characterized. We investigated PRAME expression in MCC and its relationship with Merkel cell polyomavirus (MCPyV) status, PD-L1 expression, tumor-infiltrating lymphocytes (TILs), clinicopathologic features, and clinical outcome. Thirty-five MCC cases from 3 centers were retrospectively reviewed. Histopathologic features and immunohistochemical expression of PRAME, PD-L1, MCPyV, and p53 were reassessed. PRAME positivity was defined as staining extent scores of 3+ or 4+ combined with at least moderate staining intensity. TILs were evaluated on hematoxylin and eosin sections. Clinicopathologic correlations were assessed statistically, and overall survival and distant metastasis-free survival were analyzed using Kaplan-Meier and Cox regression methods. PRAME expression was identified in 10 of 33 evaluable tumors (30.3%). Most positive cases showed diffuse nuclear staining, although one tumor demonstrated heterogeneous PRAME expression. MCPyV positivity was seen in 51.4% of cases, and PRAME expression was more frequent in MCPyV-positive tumors (P=0.057). Combined PRAME/PD-L1 positivity was associated with higher TIL density (P=0.018). PRAME expression was not associated with clinicopathologic parameters or survival. Lower PD-L1 expression (CPS <1) was independently associated with shorter overall survival. PRAME was expressed in approximately one-third of MCCs. PRAME expression was not independently associated with survival outcomes. Higher expression rates in MCPyV-positive tumors and associations with selected immune-related parameters warrant further investigation.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemistry Assays Based on Ready-To-Use Antibodies and Vendor-Recommended Protocol Settings Often Perform Suboptimally.","authors":"Dordi Lea, Ivar Skaland","doi":"10.1097/PAI.0000000000001349","DOIUrl":"10.1097/PAI.0000000000001349","url":null,"abstract":"<p><p>The use of ready-to-use (RTU) antibodies in pathology laboratories has increased due to regulatory changes and the need for standardized, efficient diagnostic workflows. This study compares the performance of RTU antibodies from 2 major suppliers, Agilent (Dako Omnis platform) and Roche (BenchMark Ultra Plus system) in a Norwegian hospital setting. A total of 125 RTU antibodies were evaluated using vendor-recommended protocol settings (VRPS) and scored according to NordiQC standards. Results showed that 58 out of 62 antibodies on the Dako Omnis platform were rated as \"optimal\" or \"good,\" compared with 37 out of 63 on the BenchMark Ultra Plus. Notably, 26 (41.3%) of Roche antibodies were rated \"borderline\" or \"poor.\" Our study shows that several RTU antibodies perform suboptimally with VRPS. This highlights the importance of thorough validation and verification of RTU antibodies before diagnostic use. The findings underscore the need for reliable protocols from manufacturers and encourage interlaboratory collaboration to improve diagnostic consistency and quality assurance.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Single-Center Comparative Study of the c-MET Immunohistochemistry SP44 and LBP4 Assays in Chinese Non-Small Cell Lung Cancer (NSCLC) Cohort.","authors":"Yan Wang, Zuoyu Liang, Siyang Song, Bingshi Liu, Hanmei Zhang, Lili Jiang, Yanyan Su, Weiya Wang","doi":"10.1097/PAI.0000000000001334","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001334","url":null,"abstract":"<p><p>c-MET is a promising therapeutic target in non-small cell lung cancer (NSCLC). This necessitates accurate detection of c-MET aberrations for effective c-MET tyrosine kinase inhibitor (TKI) therapy. Immunohistochemistry (IHC) is widely used to identify c-MET overexpression. SP44 is the most common antibody for c-MET IHC, but LBP4, a novel monoclonal antibody, offers a cost-effective alternative. This study compares LBP4 and SP44 to enhance c-MET IHC accessibility and identify NSCLC patients who may benefit from c-MET TKI therapy. LBP4 and SP44 antibodies were compared in 238 NSCLC cases from West China Hospital, with 73 specimens further analyzed for secondary antibody consistency (Ultraview vs. Optiview). c-MET IHC results were blindly evaluated by 3 pathologists. In addition, overall survival (OS) and progression-free survival (PFS) were analyzed in 51 savolitinib-treated patients. LBP4 and SP44 antibodies showed high consistency (93.7%, κ=0.908). SP44 demonstrated 97.26% concordance between Ultraview and Optiview (κ=0.9559), while LBP4 achieved 95% concordance (κ=1.0). In savolitinib-treated patients, c-MET IHC 2+/3+ cases had significantly higher OS than IHC 1+ (P=0.0035). LBP4 shows strong concordance with SP44, providing a cost-effective alternative for c-MET IHC. Ultraview secondary antibody performs comparably to Optiview. LBP4 combined with Ultraview effectively identifies NSCLC patients likely to benefit from c-MET TKI therapy, supporting c-MET IHC as a reliable screening tool and promoting its clinical application.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inter-Rater Agreement in PD-L1 (22C3) Expression Evaluation in Colon Cancer.","authors":"Dea N M Jepsen, Marianne B Jensen, Trine L Grantzau, Astrid L B Bennedsen, Thomas T Eriksen, Michael Bzorek, Ismail Gögenur, Anne-Marie K Fiehn","doi":"10.1097/PAI.0000000000001345","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001345","url":null,"abstract":"<p><p>Programmed death-ligand 1 (PD-L1) is a predictive biomarker in various cancers. In colorectal cancer, PD-L1 expression evaluation is not part of the routine examination and standardized evaluation methods are lacking. This study aimed to examine inter-rater agreement in PD-L1 expression evaluation in patients with colon cancer (CC) using different manual scoring methods, and to compare the manual methods to a digital evaluation. Two pathologists evaluated 188 PD-L1-stained slides from patients with CC. The tumor proportion score (TPS) and immune cell score (ICS) were categorized as <1%, 1-9%, and ≥10% positivity and the combined positive score (CPS) as <1, 1-9, and ≥10 positivity. Inter-rater agreement was assessed using different cutoffs and consensus scores were compared with an in-house-developed digital algorithm quantifying PD-L1. Percentage agreement was 98.9% for TPS, 85.6% for ICS, and 88.8% for CPS. When dichotomized using 1% or 10% for ICS and 1 or 10 for CPS as cutoffs, the percentage agreement increased. Only 2 cases presented with a consensus TPS ≥1%, while 96.8% had a consensus ICS of <10%, and 98.4% a consensus CPS of <10. When the digital PD-L1 score was categorized into low and high, the highest agreement with the manual evaluations was reached using the third quartile as a cutoff. Conclusively, high inter-rater percentage agreements were obtained for all scoring methods, although kappa values varied. Results comparable to the manual evaluation were reached with a digital algorithm. A digital approach can potentially eliminate inter-rater variability. Clinically relevant cutoff values remain to be determined.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Expression of RhoJ Protein in Breast Carcinoma.","authors":"Xavier Catteau, Manon Charry, Justine Allard, Sandrine Rorive, Isabelle Salmon, Jean-Christophe Noël","doi":"10.1097/PAI.0000000000001330","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001330","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common form of cancer diagnosed in women. Breast cancer cells gain the expression of mesenchymal-specific genes in a process known as epithelial-mesenchymal transition (EMT). RhoJ, a small Rho GTPase, is a key regulator that promotes resistance to a wide range of chemotherapeutic agents in epithelial-mesenchymal transition tumor cells.</p><p><strong>Methods: </strong>Sixty-three cases of invasive breast carcinoma and 10 cases of normal breast tissue were collected to examine the protein's expression of RhoJ in epithelial and stromal cells. Two pathologists performed the H-Score in a blinded fashion.</p><p><strong>Results: </strong>Normal ductal cells expressed RhoJ moderately to sometimes intensely. Normal breast stroma showed low to moderate expression in 95% of cases. All malignant ductal cells, except for 2 cases of metaplastic carcinoma, showed diffuse and intense expression. Stromal cells in invasive areas showed low to moderate expression. We found no statistically significant difference in RhoJ expression between carcinoma and normal breast tissue or between carcinoma subtypes (no special type vs. lobular; triple negative vs. luminal). Interestingly, we found a lower expression of RhoJ in metaplastic carcinomas (2 cases of spindle cell variants).</p><p><strong>Conclusions: </strong>High levels of RhoJ expression in most breast carcinomas suggest it could be a valuable therapeutic target. However, further studies involving a larger patient cohort are necessary to validate these findings.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Biomarkers in Ductal Carcinoma in Situ: An Interobserver Agreement Study.","authors":"Rachel L Stewart, Daniel S Hippe, Rebeca Alvarez, Sara H Javid, Janice N Kim, Mary Lynn Bryant, Isabella Li, Debosmita Biswas, Anum S Kazerouni, Savannah C Partridge, Habib Rahbar, Mark R Kilgore","doi":"10.1097/PAI.0000000000001335","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001335","url":null,"abstract":"<p><p>Ductal carcinoma in situ (DCIS) is a noninvasive form of breast cancer that accounts for 15% to 25% of all new breast cancer diagnoses. Clinical management approaches for DCIS include surgical excision, radiotherapy, and endocrine therapy (for patients with estrogen receptor (ER)-positive disease). Active surveillance is also being investigated for patients with low-risk disease. Pathologist assessment of nuclear grade as well as ER expression by immunohistochemistry is currently used to inform clinical decision-making. Exploratory protein biomarkers in DCIS include HER2, p16, p53, and Ki-67. Our study evaluated pathologist interreader agreement for the following immunohistochemical stains applied across 40 cases of DCIS: ER, PR, HER2, p16, Ki-67, and p53. We found that pathologist agreement was good to excellent for assessment of ER and PR (progesterone receptor), both with regard to the percent of cells staining as well as staining intensity (ICC/kappa: 0.76-0.96 for ER, 0.69-0.98 for PR). Interreader agreement was also good to excellent for HER2 interpretation (ICC/kappa: 0.78-0.97). For additional exploratory biomarkers, including p16, p53, and Ki-67, interreader agreement ranged from fair to good, likely reflecting a lack of pathologist training and less familiarity with these biomarkers in the context of DCIS. Our findings suggest that investigators should take potential interreader variability into consideration when designing clinical trials and exploratory biomarker studies.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}