PTEN in triple-negative breast carcinoma: protein expression and genomic alteration in pretreatment and posttreatment specimens

Autor: Hui Chen, Qingqing Ding, Laila Khazai, Li Zhao, Senthil Damodaran, Jennifer K. Litton, Gaiane M. Rauch, Clinton Yam, Jeffrey T. Chang, Sahil Seth, Bora Lim, Alastair M. Thompson, Elizabeth A. Mittendorf, Beatriz Adrada, Kiran Virani, Jason B. White, Elizabeth Ravenberg, Xingzhi Song, Rosalind Candelaria, Banu Arun, Naoto T. Ueno, Lumarie Santiago, Sadia Saleem, Sausan Abouharb, Rashmi K. Murthy, Nuhad Ibrahim, Mark J. Routbort, Aysegul Sahin, Vicente Valero, William Fraser Symmans, Debu Tripathy, Wei-Lien Wang, Stacy Moulder, Lei Huo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Therapeutic Advances in Medical Oncology, Vol 15 (2023)
Druh dokumentu: article
ISSN: 1758-8359
17588359
DOI: 10.1177/17588359231189422
Popis: Background: Recent advances have been made in targeting the phosphoinositide 3-kinase pathway in breast cancer. Phosphatase and tensin homolog (PTEN) is a key component of that pathway. Objective: To understand the changes in PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether PTEN copy number variation (CNV) by next-generation sequencing (NGS) can serve as an alternative to immunohistochemistry (IHC) to identify PTEN loss. Methods: We compared PTEN expression by IHC between pretreatment tumors and residual tumors in the breast and lymph nodes after neoadjuvant chemotherapy in 96 patients enrolled in a TNBC clinical trial. A correlative analysis between PTEN protein expression and PTEN CNV by NGS was also performed. Results: With a stringent cutoff for PTEN IHC scoring, PTEN expression was discordant between pretreatment and posttreatment primary tumors in 5% of patients ( n = 96) and between posttreatment primary tumors and lymph node metastases in 9% ( n = 33). A less stringent cutoff yielded similar discordance rates. Intratumoral heterogeneity for PTEN loss was observed in 7% of the patients. Among pretreatment tumors, PTEN copy numbers by whole exome sequencing ( n = 72) were significantly higher in the PTEN-positive tumors by IHC compared with the IHC PTEN-loss tumors ( p
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