TEM1 expression in cancer-associated fibroblasts is correlated with a poor prognosis in patients with gastric cancer.
The cancer stroma, including cancer-associated fibroblasts (CAFs), is known to contribute to cancer cell progression and metastasis, suggesting that functional proteins expressed specifically in CAFs might be candidate molecular targets for cancer treatment. The purpose of the present study was to explore the possibility of using TEM1 (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 TEM1 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. TEM1 expression in CAFs or vessel-associated cells was determined using immunohistochemical staining. Three items (CAF-TEM1-positivity, CAF-TEM1-intensity, and vessel-TEM1-intensity) were then examined to determine the correlations between the TEM1 expression status and the recurrence-free survival (RFS), overall survival (OS), cancer-related survival (COS), and other clinicopathological factors. Significant correlations between CAF-TEM1-positivity or CAF-TEM1-intensity and RFS, OS, or COS were observed (P < 0.001, Kaplan-Meier curves); however, no significant correlation between vessel-TEM1-intensity and RFS, OS, or COS was observed. A univariate analysis showed that CAF-TEM1-positivity and CAF-TEM1-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 TEM1 expression specifically in the CAFs of gastric carcinoma might represent a new strategy for the treatment of gastric cancer.
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Satoshi
S
Fujii
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Ayano
A
Fujihara
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Kei
K
Natori
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Anna
A
Abe
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Yasutoshi
Y
Kuboki
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Youichi
Y
Higuchi
Department of Digestive Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishicho, Chuou-ku, Niigata, 951-8566, Japan.
Masaki
M
Aizawa
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Takeshi
T
Kuwata
Department of Surgical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Takahiro
T
Kinoshita
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Minami-ku, Hiroshima, 734-8551, Japan.
Wataru
W
Yasui
Pathology Division, Research Center for Innovative Oncology National Cancer Center at Kashiwa, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Atsushi
A
Ochiai
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D055815:Young Adult
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C078203:CD248 protein, human
Cancer stromal cell; TEM1; cancer-associated fibroblast; gastric cancer; immunohistochemistry