Abstract 1799: CRM1 expression in pancreatic adenocarcinoma correlates with survivin expression and the proliferative activity

Abstract Introduction: CRM1 is a nuclear export chaperone that mediates the export of proteins essential to growth regulation and tumor suppression. Its overexpression in tumors was found to be associated with poor prognosis. Selective inhibitors of nuclear export are in phase I and II clinical trials for several tumor types. The expression of CRM1 in human pancreatic adenocarcinoma (PAC) and its relation to survivin expression and tumor proliferative activity is largely unknown. Experimental procedures: Sections of tissue microarray containing 77 formalin fixed and paraffin embedded PAC were stained by immunohistochemistry (IHC) for CRM1, survivin, and Cyclin A. Expression levels of CRM1 and survivin in tumor cells was determined using a quantitative digital image analysis solution (OTMIAS). The tumor proliferative activity was determined by measuring the S-phase fraction (SPF) in sections stained for Cyclin A, also using OTMIAS. Summary: Sixty-six of the 77 (86%) PAC showed at least some positive staining for CRM1, and 11 (14%) were completely negative. The mean CRM1 expression levels ranged from 0.3 to 53 units and the median from 0.3 to 45 units. There was significant positive correlation between the mean and median expression levels of CRM1 in tumor cells with the mean and median levels of survivin (p<0.001). Moreover, there was positive correlation between the mean and median CRM1 levels in tumor cells the SPF (p=0.005). Conclusions: CRM1 is expressed in a significant proportion of PAC, and increased CRM1 expression correlates with increased survivin expression and increased proliferative activity, suggesting that selective inhibitors of nuclear export may be effective against PAC. Note: This abstract was not presented at the meeting. Citation Format: David M. Saulino, Pamela S. Younes, Jennifer M. Bailey, Mamoun Younes. CRM1 expression in pancreatic adenocarcinoma correlates with survivin expression and the proliferative activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1799. doi:10.1158/1538-7445.AM2017-1799