Expression and Clinical Significance of &amp;lt;i&amp;gt;PIK3CA&amp;lt;/i&amp;gt;, &amp;lt;i&amp;gt;c-MET&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;c-KIT&amp;lt;/i&amp;gt; Mutations in Saudi Breast Cancer Patients

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

doi:10.4236/abcr.2021.103005

Expression and Clinical Significance of &lt;i&gt;PIK3CA&lt;/i&gt;, &lt;i&gt;c-MET&lt;/i&gt; and &lt;i&gt;c-KIT&lt;/i&gt; Mutations in Saudi Breast Cancer Patients

Rami Nassir, Hanan M Abd Elmoneim + Show 3 more

Open Access

https://doi.org/10.4236/abcr.2021.103005

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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.

Highlights

Breast cancer is one of the most common tumors that intimidate women’s health
phosphatase and Tensin-Homolog (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

Summary

Introduction

Breast cancer is one of the most common tumors that intimidate women’s health. It accounts alone for 30% of all new cancer cases in women. The death rate for breast cancer decreased by 40% from 1989 to 2016, breast cancer leads to cancer deaths among women aged 20 to 59 years. In Saudi Arabia, breast cancer is one of the most frequent malignancies among women between the age of 20 and 60. Triple negative breast cancer (TNBC) is marked by bad prognosis and low survival rate regardless of the effectiveness of hormonal therapies. In Saudi population, TNBC patients who are HER2 positive have a high grade and large tumor size at presentation especially for women who are under the age of 50 years [4]

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