Open AccessTEM 1 expression in cancer‐associated fibroblasts is correlated with a poor prognosis in patients with gastric cancer
Author(s) -
Fujii Satoshi,
Fujihara Ayano,
Natori Kei,
Abe Anna,
Kuboki Yasutoshi,
Higuchi Youichi,
Aizawa Masaki,
Kuwata Takeshi,
Kinoshita Takahiro,
Yasui Wataru,
Ochiai Atsushi
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.515
Subject(s) - cancer , immunohistochemistry , cancer cell , stroma , metastasis , lymphovascular invasion , medicine , pathology , cancer associated fibroblasts , tissue microarray , lymphatic system , lymphatic vessel , staining
The cancer stroma, including cancer‐associated fibroblasts ( CAF s), is known to contribute to cancer cell progression and metastasis, suggesting that functional proteins expressed specifically in CAF s might be candidate molecular targets for cancer treatment. The purpose of the present study was to explore the possibility of using TEM 1 (tumor endothelial marker 1), which is known to be expressed in several types of mesenchymal cells, as a molecular target by examining the impact of TEM 1 expression on clinicopathological factors in gastric cancer patients. A total of 945 consecutive patients with gastric cancer who underwent surgery at the National Cancer Center Hospital East between January 2003 and July 2007 were examined using a tissue microarray approach. TEM 1 expression in CAF s or vessel‐associated cells was determined using immunohistochemical staining. Three items ( CAF ‐ TEM 1‐positivity, CAF ‐ TEM 1‐intensity, and vessel‐ TEM 1‐intensity) were then examined to determine the correlations between the TEM 1 expression status and the recurrence‐free survival ( RFS ), overall survival ( OS ), cancer‐related survival ( COS ), and other clinicopathological factors. Significant correlations between CAF ‐ TEM 1‐positivity or CAF ‐ TEM 1‐intensity and RFS , OS , or COS were observed ( P < 0.001, Kaplan–Meier curves); however, no significant correlation between vessel‐ TEM 1‐intensity and RFS , OS , or COS was observed. A univariate analysis showed that CAF ‐ TEM 1‐positivity and CAF ‐ TEM 1‐intensity were each correlated with a scirrhous subtype, tumor depth, nodal status, distant metastasis, serosal invasion, lymphatic or venous vessel infiltrations, and pTMN stage. This study suggests that the inhibition of TEM 1 expression specifically in the CAF s of gastric carcinoma might represent a new strategy for the treatment of gastric cancer.