Abstract

Role of BRCA1 and PARP1 has been studied by immunohistochemistry in a cohort of ovarian cancers. Their expression has been related to overall survival and disease free disease.
Objective: To investigate the clinical outcome of an heterogeneous population of ovarian cancers as respect to immunohistochemical expression of BRCA1 and PARP1 in order to identify a histological threshold for positivity and negativity and to predict possible candidates to anti-PARP therapy
Material and methods: 97 cases of ovarian cancers were collected in a multicentre study and immunohistochemically tested for BRCA1 and PARP1. The immunohistochemical expression of BRCA1 and PARP1 was studied on formalin-fixed and paraffin-embedded samples. Overall survival and disease free survival were evaluated. Statistical analysis was performed including cancers of all types and a subgroup of high grade serous carcinoma that represents the predominant histotype.
Results: A possible threshold to discriminate positive and negative cases has been proposed. BRCA1 and PARP1 immunohistochemical expression did not significantly correlate with overall survival. The evaluation of survival for the combinations of BRCA1+/-, PARP1+/- showed a longer patient survival when the positivity and negativity were in contrast compared to when they were in agreement.
Conclusions: Although BRCA1 and PARP1 expression do not appear to be correlated with overall survival, further investigation and follow-up together with a larger number of cases could clarify the function; the standardised immunohistochemical method could better select the patient group sensitive to PARP1 inhibitors.

Keywords: Ovarian cancer; BRCA1; PARP1; Immunohistochemistry; Overall survival; Disease free survival; Anti- PARP therapy