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has been cited by the following article:

• TITLE: Expression and Clinical Significance of PIK3CA, c-MET and c-KIT Mutations in Saudi Breast Cancer Patients

  AUTHORS: Rami Nassir, Ghada Esheba, Hanan M. Abd Elmoneim, Ahlam S. Altowairqi, Ghassan Nouman

  KEYWORDS: PTEN, PIK3CA, c-MET, c-KIT, Breast Cancer

  JOURNAL NAME: Advances in Breast Cancer Research, Vol.10 No.3, July 6, 2021

  ABSTRACT: Objective: PIK3CA is the most common pathway affected by mutations in breast cancer. PIK3CA/PTEN pathway is under intense investigation as a possible target for molecular therapy. Dysregulation PIK3CA/PTEN pathway is a substantial mechanism for the development of resistance to anti-HER2 therapy. Therefore, we aimed to study the PIK3CA/PTEN in breast cancer patients in Saudi population. Methods: We applied PTEN immunohistochemistry on 98 patients. Then, we applied next-generation sequencing to determine the genetic variations associated with the development of breast cancer and their correlations with clinicopathological variables. Results: PTEN expression was significantly correlated with lymph node metastasis (LNM), tumor stage, lymphovascular invasion (LVI) and triple negative breast cancer (TNBC). The prevalence of the PIK3CA mutation was 33.3% of cases and it was significantly associated with LNM, tumor stage, and with PTEN expression. c-MET mutation was identified in 41.7% of cases and it was associated with tumor stage and with TNBC, while c-KIT mutation was detected in 20.8% of cases, and it was significantly associated with TNBC only. Patients with positive PTEN expression had a significantly better overall survival (OS); on the contrary, patients with PIK3CA and c-MET had a significantly worse OS. Conclusion: Our study confirms the importance of PIK3CA/PTEN pathway in breast cancer patients. A high frequency of PIK3CA and c-MET mutations was detected and was associated with poor prognosis. Both c-MET and c-KIT genes have significant roles in developing TNBC. These findings should be expanded to a larger group study to improve the clinical outcomes and individualizing treatment.