Academic Journal
PTEN in triple-negative breast carcinoma: protein expression and genomic alteration in pretreatment and posttreatment specimens
| العنوان: | PTEN in triple-negative breast carcinoma: protein expression and genomic alteration in pretreatment and posttreatment specimens |
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| المؤلفون: | Chen, Hui, Ding, Qingqing, Khazai, Laila, Zhao, Li, Damodaran, Senthil, Litton, Jennifer K., Rauch, Gaiane M., Yam, Clinton, Chang, Jeffrey T., Seth, Sahil, Lim, Bora, Thompson, Alastair M., Mittendorf, Elizabeth A., Adrada, Beatriz, Virani, Kiran, White, Jason B., Ravenberg, Elizabeth, Song, Xingzhi, Candelaria, Rosalind, Arun, Banu, Ueno, Naoto T., Santiago, Lumarie, Saleem, Sadia, Abouharb, Sausan, Murthy, Rashmi K., Ibrahim, Nuhad, Routbort, Mark J., Sahin, Aysegul, Valero, Vicente, Symmans, William Fraser, Tripathy, Debu, Wang, Wei-Lien, Moulder, Stacy, Huo, Lei |
| المساهمون: | Winterhof and Still Water funds, Philanthropic funds to the Moon Shots Program of the University of Texas MD Anderson Cancer Center, CPRIT Multi-Investigator Research Award |
| المصدر: | Therapeutic Advances in Medical Oncology ; volume 15 ; ISSN 1758-8359 1758-8359 |
| بيانات النشر: | SAGE Publications |
| سنة النشر: | 2023 |
| الوصف: | 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 < 0.0001). However, PTEN-positive and PTEN-loss tumors by IHC overlapped in copy numbers: 14 of 60 PTEN-positive samples showed decreased copy numbers in the range of those of the PTEN-loss tumors. Conclusion: Testing various specimens by IHC may generate different PTEN results in a small proportion of patients with TNBC; therefore, the decision of testing one versus multiple specimens in a clinical trial should be defined in the patient inclusion criteria. Although a distinct cutoff by which CNV differentiated PTEN-positive tumors from those with PTEN loss was not identified, higher copy number of PTEN may confer positive PTEN, whereas lower copy number of PTEN would ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1177/17588359231189422 |
| الاتاحة: | https://doi.org/10.1177/17588359231189422 https://journals.sagepub.com/doi/pdf/10.1177/17588359231189422 https://journals.sagepub.com/doi/full-xml/10.1177/17588359231189422 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.F03732AA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1177/17588359231189422 |
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