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.