Abstract
CRM1/XPO1 (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. Our aim was to investigate CRM1 expression in pancreatic adenocarcinoma (PAC) and its relationship to survivin expression and the proliferative activity. Sections of tissue microarray containing 76 formalin fixed and paraffin embedded PAC were stained by immunohistochemistry (IHC) for CRM1, survivin, and Cyclin A. Expression levels of CRM1 and survivin and the proliferative activity, the S-phase fraction (SPF) in tumor cells, were determined using a quantitative digital image analysis solution (OTMIAS). Sixty-six of the 76 (86%) PAC showed positive staining for CRM1, and 10 (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 and 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 and the SPF (p=0.013). Our results show that CRM1 is expressed in a significant proportion of PAC, and increased CRM1 levels correlates with increased survivin levels and increased proliferative activity.
Highlights
Pancreatic adenocarcinoma (PAC) is an aggressive malignancy with a dire prognosis
Our results show that CRM1 is expressed in a significant proportion of pancreatic adenocarcinoma (PAC), and increased CRM1 levels correlates with increased survivin levels and increased proliferative activity
The aim of this study was to 1) determine whether CRM1 is expressed in human PAC and 2) whether this expression correlates with the expression of survivin and tumor proliferative activity as surrogates of CRM1 activity
Summary
Pancreatic adenocarcinoma (PAC) is an aggressive malignancy with a dire prognosis. About 40% of patients diagnosed with PAC will present at an advanced stage, resulting in very limited treatment choices and difficult clinical decisions [2]. CRM1 was found to be overexpressed in several types of transformed cells and malignant tissues, and its overexpression correlates with aggressive behavior and poor survival [3]. CRM1 regulates survivin, which is involved in the regulation of mitosis and other important www.oncotarget.com functions related to cell survival. The aim of this study was to 1) determine whether CRM1 is expressed in human PAC and 2) whether this expression correlates with the expression of survivin and tumor proliferative activity as surrogates of CRM1 activity
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