Molecular differential diagnosis of pancreaticobiliary cancers and markers that predict their treatment efficacy

Pancreaticobilliary cancers are poor prognosis cancers with decreased outcome despite improvements in modern treatments. Struggles in differential diagnosis are common in tumors arising from this region. Especially in ampullary tumors it is usually hard to find out the origin of tumor. However the origin of tumor is very important in the treatment decision. In addition, we did not have yet any predictor marker for treatment utility and prognosis in ampullary tumors. To know which patients will benefit more from chemotherapy will also decrease treatment toxicity. For this reason, the aim of our study is to find out the differential diagnosis for the origin of ampullary carcinoma from pancreaticobilliary cancers (duodenal ductus, pancreatic ductus or billiary ductus) with molecular methods and investigate predictor markers that can predict the efficiency of treatment protocols in these tumors. In our study, paraffin blocks of patients with ampulla cancer followed by İzmir Katip Çelebi University Atatürk Training and Research Hospital Medical Oncology Clinic between years 2006-2016 will be obtained. MUC1, MUC2, MUC5AC, CDX2, Cytokeratin 7, Cytokeratin 20, PD-1, PD-L1 were analyzed immunohistochemically from these tissues, and EGFR was analyzed by PCR. Only the patients whose data are available were included. It will be evaluated whether these markers predict the survival of the patients and the effectiveness of the treatments given. The median age of the cases in our study was 61 (39-79). Sixty-48 (57.8%) were male and 35 (42.2%) were female. Stages of patients; 2 patients (2.4%) for Stage IA, 19 patients (22.9%) for Stage IB, 17 patients (20.5%) for Stage IIA, 5 patients (6.0%) for Stage IB, 28 patients (33.7%) for Stage IIIA and 12 patients (14.5%) for Stage IIIB. According to our haematoxylene eosin and CAP dual/triple system evaluation, 27 cases were accepted as pancreaticobiliary and 56 were intestinal. When we compared PDL1 and PD1 IHC staining, 19.6% (n:11), 26.7% (n:15) of intestinal type tumors and 25.9% (n:7), 29.6% (n:8) of pancreaticobiliary type tumors, was found to be positive respectively. EGFR mutation was detected in a total of 6 patients and 5 of these 6 mutations were shown in intestinal type and 1 in pancreaticobiliary type. The median OS of patients with intestinal type adenocarcinoma was 23 months, while the median survival of patients with pancreaticobiliary adenocarcinoma was 76. When the survival of PD1 positive, PDL1 positive patients and PD1 negative, PDL1 negative patients were compared, no significant difference was found (p:0.118; p:0.884). A significant difference was found in terms of both OS and DFS in the survival of patients with EGFR mutations compared to those without (p:0.08; p:0.010). It was observed that adjuvant therapy did not contribute to the median survival of patients (p:0.741), but first-line chemotherapy significantly prolonged the survival of patients (p:0.000). In our study, we also confirmed that intestinal and pancreaticobiliary subtypes of ampullary adenocarcinoma have different clinical course and prognosis. We determined that EGFR mutation may have a prognostic role. We have seen that chemotherapy, not adjuvant, but in the metastatic period, contributes to the survival of the patients. However, considering that there are limited clinical studies on these rare tumors, it is clear that many studies are required in terms of both differential diagnosis of its subtypes and their treatment.