Xiao Huang, Shuko Harada, Shi Wei, Gene P Siegal, Sarah A Anderson, Aysegul A Sahin, Katia Khoury, Ceren Yalniz
{"title":"Association between p16<sup>INK4A</sup> expression and a treatment response to CDK4/6 inhibitor in advanced breast carcinoma.","authors":"Xiao Huang, Shuko Harada, Shi Wei, Gene P Siegal, Sarah A Anderson, Aysegul A Sahin, Katia Khoury, Ceren Yalniz","doi":"10.1016/j.humpath.2025.105905","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Endocrine therapy combined with cyclin-dependent kinase 4 and 6 inhibitors (1) has been approved for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast carcinomas. It has been known that the p16-CDK4/6-cyclin D1 axis regulates the S phase of the cell cycle. We investigated the association between p16 expression and the therapeutic response with CDK4/6i in advanced breast carcinoma.</p><p><strong>Methods: </strong>Patients diagnosed with invasive breast carcinoma between 2019 and 2024 whose tumors underwent next-generation sequencing (NGS) based analysis were identified. The expression of p16 was assessed in tumor cells and stromal cells within the invasive carcinoma by immunohistochemistry. In tumor cells, p16 expression was subclassified as cytoplasmic (TC), nuclear (TN), or cytoplasmic and nuclear staining (TCN). In stromal cells, p16 expression was assessed in tumor-associated fibroblasts (TAF) and tumor-infiltrating immune cells (TILs) in any cellular compartment.</p><p><strong>Results: </strong>Among the 35 cases, p16-TC, -TN, and -TCN were significantly associated with disease progression during CDK4/6i therapy. The positive association between p16-TC and progressive disease remained in the 24 CDK4/6i-treatment naïve tumors. In contrast, the tumors with p16 expression in TAF showed a numerically higher response rate than the p16-TAF-negative ones. We also observed a significant association between p16-TC expression and lymph node metastasis.</p><p><strong>Conclusion: </strong>Our study demonstrated a significant association between p16 expression in tumor cells and an unfavorable therapeutic response to CDK4/6i in advanced breast carcinoma. The clinical significance of p16 expression patterns as a predictive biomarker for CDK4/6i deserves further investigation.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105905"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.humpath.2025.105905","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/7 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Endocrine therapy combined with cyclin-dependent kinase 4 and 6 inhibitors (1) has been approved for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast carcinomas. It has been known that the p16-CDK4/6-cyclin D1 axis regulates the S phase of the cell cycle. We investigated the association between p16 expression and the therapeutic response with CDK4/6i in advanced breast carcinoma.
Methods: Patients diagnosed with invasive breast carcinoma between 2019 and 2024 whose tumors underwent next-generation sequencing (NGS) based analysis were identified. The expression of p16 was assessed in tumor cells and stromal cells within the invasive carcinoma by immunohistochemistry. In tumor cells, p16 expression was subclassified as cytoplasmic (TC), nuclear (TN), or cytoplasmic and nuclear staining (TCN). In stromal cells, p16 expression was assessed in tumor-associated fibroblasts (TAF) and tumor-infiltrating immune cells (TILs) in any cellular compartment.
Results: Among the 35 cases, p16-TC, -TN, and -TCN were significantly associated with disease progression during CDK4/6i therapy. The positive association between p16-TC and progressive disease remained in the 24 CDK4/6i-treatment naïve tumors. In contrast, the tumors with p16 expression in TAF showed a numerically higher response rate than the p16-TAF-negative ones. We also observed a significant association between p16-TC expression and lymph node metastasis.
Conclusion: Our study demonstrated a significant association between p16 expression in tumor cells and an unfavorable therapeutic response to CDK4/6i in advanced breast carcinoma. The clinical significance of p16 expression patterns as a predictive biomarker for CDK4/6i deserves further investigation.
期刊介绍：
Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.
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