p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency

被引:0
作者
Lee, Miseon [1 ]
Lee, Ahwon [1 ,2 ]
Choi, Byung-Ock [3 ]
Park, Woo-Chan [4 ]
Lee, Jieun [5 ]
Kang, Jun [1 ]
机构
[1] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Hosp Pathol, Seoul, South Korea
[2] Catholic Univ Korea, Canc Res Inst, Seoul, South Korea
[3] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Radiat Oncol, Seoul, South Korea
[4] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Surg,Div Breast Surg, Seoul, South Korea
[5] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Internal Med,Div Med Oncol, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
Triple-negative breast cancer; p16; immunohistochemistry; RB pathway; pRB-deficient tumor; RB TUMOR-SUPPRESSOR; CELL LUNG-CANCER; HOMOLOGOUS RECOMBINATION; NEOADJUVANT CHEMOTHERAPY; PATHWAY; EXPRESSION; PROTEIN; ASSOCIATION; RESISTANCE; INHIBITOR;
D O I
10.1159/000541299
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Introduction: Triple-negative breast cancer (TNBC) is associated with alterations in the retinoblastoma pathway. As a consequence of retinoblastoma protein (pRB) loss, compensatory upregulation of p16 occurs due to the loss of phosphorylated pRB-mediated negative feedback on p16 expression. The aim of this study is to investigate the clinicopathological and genomic characteristics associated with the diffuse pattern of p16 immunohistochemistry (IHC) in TNBC. Methods: The study analyzed surgically resected TNBC for whole-exome sequencing in 113 cases and for cDNA microarray in 144 cases. The p16 IHC results were classified into two patterns: diffuse and negative/mosaic. Results: In the entire cohort (n = 257), the diffuse pattern of p16 IHC was observed in 123 (47.9%) patients and the negative/mosaic pattern in 134 (52.1%). Biallelic RB1 inactivation was observed in 14.3% of patients with the diffuse pattern. The diffuse pattern of p16 IHC showed more frequent RB1 alterations and cell cycle progression signatures, a higher Ki-67 labeling index, more frequent chromosome segment copy number changes, a higher frequency of homologous recombination deficiency high, and immune- related signatures. PIK3CA mutations were more frequent in the negative/mosaic pattern. CCND1 amplification was identified in 5 cases, all with the negative/mosaic pattern. Conclusion: In TNBC, the diffuse p16 pattern shows clinical and genomic similarities to pRB-deficient tumors, suggesting shared characteristics. This suggests that p16 IHC testing may provide new therapeutic approaches, underscoring its potential clinical importance. (c) 2024 The Author(s). Published by S. Karger AG, Basel
引用
收藏
页码:63 / 76
页数:14
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