Journal of International Research in Medical and Pharmaceutical Sciences
 

Journal of International Research in Medical and Pharmaceutical Sciences, ISSN No. : 2395-4477 (Print), 2395-4485 (Online), Vol.: 11, Issue.: 4

Original Research Article

CLINICOPATHOLOGICAL SIGNIFICANCE OF ELEVATED PIK3CA AND AKT EXPRESSION IN BREAST CANCER MOLECULAR SUBTYPES AMONG WEST ALGERIAN PATIENTS

 

AMINA BENDAOUD1, LYNDA ADDOU-KLOUCHE1,2*, AMINA BELHADJ1, MERIEM KAOUTER BENYELLES1, BADRA ZAKMOUT1, BELKACEM KELKOUL3, BOUAKLINE HOUSSEM3, MOHAMED BENALI1,4 AND SORAYA MOULESSEHOUL1,4

1Department of Biology, Djillali Liabes University of Sidi bel Abbes, Algeria.

2Laboratory of Applied Molecular Biology and Immunology, University of Abou Bekr Belkaid, Tlemcen, Algeria.

3Anatomy and Pathology Laboratory, Regional Military Hospital, Algeria.

4Laboratory of Biotoxicology, Djillali Liabes University of Sidi bel Abbes, Algeria.

Abstracts

Background: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer, apparently with different biologic impact on specific cancer subtypes. It has been suggested that the deregulation of PI3K/AKT pathway promotes resistance to chemotherapy, trastuzumab, and tamoxifen. This suggests that targeting the PI3K/Akt pathway may increase the therapeutic efficacy of breast cancer.

We investigated PIK3CA and AKT expression in breast cancer and explored the relation ships between the PIK3CAand AKT expression level and clinicopathological features as well as breast cancer molecular subtypes.

Materials and Methods: Sixty five primary breast cancer samples were collected from the department of pathology at Oran military Hospital in western Algeria between January 2009 and December 2014. We examined PIK3CAand p- Akt expression by immunohistochemistry on formalin-fixed paraffin embedded tissues from 65 breast tumorsand reviewed patients' medical records.Associations between PIK3CAand AKT expression with clinicopathological variables and breast cancer molecular subtypes were investigated.

Results: Positive PIK3CA and p-Akt staining was observed in 50 (77%) and 18 (27.7%) breast cancer patients respectively. High expression of p-Akt was significantly associated with HER2 overexpression, ER and PR negative, and HER2 positive classes (P<0.05). Association was identified between the PIK3CA overexpression and a higher score of p-Akt (P= 0.05).

Positive PIK3CA expression was associated with aggressive tumors and clinicopathological features, such ashigh SBR grade and tumors that do not express hormone receptors ER and PR (p= 0,007 and p=0,009 respectively), Increased PIK3CA expression was associated with triple negative breast cancer (TNBC) and HER2-positive tumors (p= 0,02 ). Luminal subtype showed reduced PIK3CA expression relative to other breast cancer molecular subtypes, Tumors expressing PIK3CA are significantly associated with the expression of pAKT.

Conclusions: Our data shows that PI3K/AKT pathway activation is an oncogenic biomarker associated with poor prognosis in BC. Although, PIK3CA and pAkt overexpression was more prevalent in TNBC and HER2 positive tumors, thus targeting of PI3K/Akt pathway using specific inhibitors might be helpful in order to select patients who would benefit from current targeted therapy strategies.

Keywords :

PIK3CA; pAKT; breast cancer; immunohistochemistry; biomarker; targeted therapy.