Evaluation of relationship between BRCA1, BRCA2 and ATM expression and chemotherapy response and survival in patients with pancreatic cancer

In this study, we aimed to evaluate the expression of BRCA1, BRCA2, ATM in tumor tissue with immunohistochemistry (IHC) in patients with resected pancreatic cancer and association with prognosis and effectiveness of platinum-based treatments. One hundred thirty patients over the age of 18 with resected non-metastatic pancreatic cancer in Hacettepe University Hospital between 2005 and 2017 were included in the study. Demographic and clinicopathological features of the patients and IHC expression of BRCA1, ATM and TP53 in tumor tissues were evaluated. BRCA2 expression could not be evaluated because of the technical reasons. 46 patients (42%) had low BRCA1 expression, 25 patients (23%) had loss of ATM expression, 66 patients (62%) had abnormal TP53 expression. According to the expression of BRCA1 and ATM, there was no difference in OS and DFS between the groups (BRCA1 expression low vs high; OS:23,1 vs 16,2 mo p=0,17, DFS:16,8 vs 10,6 mo, p=0,12 ; ATM expression negative vs positive; OS:19 vs 21,9 mo, p=0,92, DFS: 11,4 vs 14,9 mo, p= 0,84). Patients with abnormal TP53 expression had longer OS (23,1 vs 15,5 mo, p=0,034) and DFS (14,1 vs 9,2 mo, p=0,025) compared to those with normal expression. Among patients with low BRCA1 or no ATM expression, there was no difference in OS and DFS between the patients who received or did not receive platinum agents. Multivariate analysis showed that disease stage, high post- op CA19-9 level, presence of thrombosis, diabetes and abnormal TP53 expression were independently associated with overall survival, whereas disease stage, high post-op CA19-9 level, presence of vascular invasion, diabetes and abnormal TP53 were associated with disease free survival. In conclusion, expression of BRCA1 and ATM with IHC in patients with resected pancreatic cancer is not useful in determining the prognosis and choosing the treatment. Evaluation of TP53 with IHC might have prognostic value.