Characterization of PI3KCA and BRAF mutations in gastric adenocarcinoma: An approach to a personalized targeted therapy for Moroccan HER2 overexpressed patients

Background and study aims

Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of PI3KCA and BRAF mutations in Moroccan HER2 overexpressed patients, in order to introduce targeted therapy in the arsenal of therapeutic modalities for management in Morocco.

Patients and methods

98 gastric adenocarcinoma tissue samples were collected. Further histological and immunohistochemical examinations were carried out at the Laboratory of Anatomy Pathology in Pasteur Institute-Morocco, in order to select HER2 positive cases. Out of 98 cases, 16 were found to be HER2-positive. The molecular study was performed for 55 good quality tissue samples including the HER2-positive ones, and activating mutations in H1047R PI3KCA and V600E BRAF were analyzed by Cast-PCR and Real-time PCR, respectively, at the Department of Molecular Biology, ANOUAL Specialized Center-Casablanca, Morocco. Statistical analyses were performed using the Epi-info software (version 6.09).

Results

Pi3KCA mutation was present in 8 cases (14,54%). BRAF mutation was present in 4 cases (7,27%) and 3 cases showed concomitant mutations. In total, 9 cases (16,36%) had PI3KCA and/or BRAF mutations.

Conclusion

The association between HER2 expression and PI3KCA alteration in gastric adenocarcinoma is most probably necessary to identify trastuzumab responders. Consequently, the 83,64% rate of HER2-positive patients harboring wild-type mutations possibly represents the portion of patients responding to trastuzumab while the 16,36% rate of patients carrying at least one of the studied mutations represents the portion of potentially non responsive patients to the targeted therapy, and thus may be considered as good candidates for multi-drug targeted therapy.