α-smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study

Item Type:	Article
Title:	α-smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study
Creators Name:	Sinn, M. and Denkert, C. and Striefler, J.K. and Pelzer, U. and Stieler, J.M. and Bahra, M. and Lohneis, P. and Doerken, B. and Oettle, H. and Riess, H. and Sinn, B.V.
Abstract:	Background: Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin ({alpha}-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of {alpha}-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients. Methods: CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of {alpha}-SMA expression and stromal density impact on patient outcome. Results: High {alpha}-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, {alpha}-SMA and stromal density expression were independently predictive factors for survival. Conclusions: Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.
Keywords:	Pancreatic Cancer, Stroma, {alpha}-SMA, Adjuvant Therapy, Gemcitabine, CONKO-001
Source:	British Journal of Cancer
ISSN:	0007-0920
Publisher:	Nature Publishing Group
Volume:	111
Number:	10
Page Range:	1917-1923
Date:	11 November 2014
Additional Information:	Copyright © 2014 Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Official Publication:	https://doi.org/10.1038/bjc.2014.495
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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