Introduction/Background Ovarian cancer ranks third among female malignancies with increasing incidence in Pakistan. BRCA-deficient cells are 1000-times more sensitive to PARP inhibitors than wild type cells. The objective of the study is to determine mutations in cancer susceptibility genes, in SEOC cases and also to evaluate PARP protein expression before and after the treatment.
Methodology 47 consenting SEOC patients were observed for 06 months after completion of therapy for chemotherapeutic response. Snapped frozen tissue was used for the genomic analysis using gene specific primers. For PARP protein ELISA and immunohistochemistry was done.
Results 86.7% of the patients were sensitive to chemotherapy whereas 13.3% showed resistance. Genetic variants of BRCA1 in 7%, BRCA2 in 4.7%, PIK3CA in 9.3%, PALB2 in 7%, CHEK2 in 2.3%, BAP1 in 2.3%, and CTNNB1 in 2.3% of the patients were found. There was also a significant association between TNM stage and the treatment response (p<0.01). Of the patients with no mutations, 90.9% showed chemosensitivity as opposed to 70% in mutations group. The median PARP concentration was higher in patients having low grade tumours and showing chemosensitivity compared to those with high grade and resistance to therapy (p = .509, p=.188) which was related to serum CA125 levels. Likewise, the median concentration decreased with increase in the tumour stage (p = .729). Patients who had mutations showed 4.29 times higher odds to resistance compared to those who had no mutation (p = .113). Similarly, The odds of resistance were 5.67 times higher in patients who were BRCA positive compared to those who were negative.
Conclusion Our study exhibits the pivotal role of genetic analysis and PARP expression in SEOC cases in predicting the treatment response and paving pathway for patient tailored targeted therapy.
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