Abstract 3000: MicroRNA-21 as a biomarker for benefit from adjuvant therapy in resectable pancreatic adenocarcinoma

Abstract

Abstract Many pancreatic adenocarcinoma patients who undergo surgical resection receive adjuvant chemotherapy and/or combined modality treatment. However, only a subset of patients benefit from additional therapy. The aim of this study was to evaluate the expression of several potential markers of treatment outcome. Resected tumors of a cohort of 82 pancreatic adenocarcinoma patients from Korea were analyzed for protein expression of 20 markers by immunohistochemistry and expression of 7 microRNAs using quantitative real-time PCR. A second validation cohort of 45 resected Italian patients was analyzed for microRNA-21 (miR-21) expression. Korean and Italian cases consisted of FFPE and frozen specimens, respectively. Univariate and multivariate analyses were used to compare biological parameters and survival endpoints. In the Korean cohort, Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N=52) showed that lower than median miR-21 expression was associated with a significantly lower HR for death (0.316; 95% CI: 0.166-0.600; p-value: 0.0004) and recurrence (0.521; 95% CI: 0.280-0.967; p-value: 0.04). Expression status of miR-21 was the single most predictive biomarker for treatment outcome from all factors evaluated. No significant association of miR-21 expression status with prognosis was detected in patients not treated with adjuvant therapy. In the independent cohort of 45 Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was also significantly correlated with longer overall and disease-free survival confirming its predictive value. Concluding, low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of pancreatic cancer cases, using both FFPE and frozen tumor specimens. These data provide evidence that miR-21 expression may allow stratification of pancreatic cancer patients for adjuvant treatment. This is the first strong predictive marker for adjuvant therapy in radically resected pancreatic cancer and further prospective studies are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3000.