Investigation of prognostic and predictive factors in malignant epithelial cancer treated with platinium and/or gemsitabine based chemotherapy

Purpose: Novel molecular biomarkers are necessary in order to predict treatment response and to estimate prognosis in cancer. ERCC1 and RRM1 are proteins which are associated in DNA repair mechanisms in normal and malignant epithelial tumor cells. The role of these proteins on tumor cell behavior and drug resistance have been intensively investigated in certain advanced stage cancer. We aimed to explore RRM1 and ERCC1 expressions in tumor cells to predict the chemotherapy response and the prognosis in patients with lung, ovarian and pancreatic cancers treated with platinium and/or gemcitabine based regimens.Material and Method: Among the all patients treated with platinium and/or gemsitabine only lung, ovarian and pancreatic cancer were selected from the archieve of Çukurova University Hospital. Tissue samples were obtained from parafine blocks and evaluated for RRM1 and ERCC1 expression with immunohistochemical method in the pathology department. The results were corelated with clinical findings and therapy response.Findings: Of the patients taken into the study 47 (51%) were lung cancer, 27 (30%) were epithelial ovarian cancer, 17 (19%) were pancreatic cancer. When compared to high ERCC1 expression in tumor cells, the low ERCC1 exprerssion showed high tumor response rates in patients with lung cancer (62% vs 29%, p=0.028) and epithelial ovarian cancer (90% vs 19%, p=0.044) but not in patients with pancreatic cancer. On the other hand, low RRM1 expression in tumor cells indicated high tumor response in patients with lung cancer (60% vs 25%, p=0.020) and pancreatic cancer (82% vs 18%, p=0.018) when compared to high RRM1 expressions. From the view of prognosis, low expression of RRM1 in patients with both lung and pancreatic cancer and also low expression of ERCC1 in only lung cancer were found significantly corelated to longer over all survival (respectively 15 vs 9, 18 vs 7 and 18 vs 9 months).Result: ERCC1 expression in lung and RRM1 expression in both lung and pancreatic cancer seem to be important prognostic factors. More importantly, we recommend to investigate ERCC1 expression for especially platinium response in lung and ovarian cancers and also RRM1 expression for especially gemcitabine response in pancreatic cancers before treatment decision.Key words: lung, ovarian, pancreas cancer, ERRC1, RRM1, prognostic and predictive factors