Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 28, 2011; 17(44): 4867-4874
Published online Nov 28, 2011. doi: 10.3748/wjg.v17.i44.4867
Vascular endothelial growth factor 165b expression in stromal cells and colorectal cancer
Makoto Tayama, Tomohisa Furuhata, Yoshiko Inafuku, Kenji Okita, Toshihiko Nishidate, Toru Mizuguchi, Yasutoshi Kimura, Koichi Hirata
Makoto Tayama, Tomohisa Furuhata, Yoshiko Inafuku, Kenji Okita, Toshihiko Nishidate, Toru Mizuguchi, Yasutoshi Kimura, Koichi Hirata, the First Department of Surgery, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan
Author contributions: Tayama M and Furuhata T contributed equally to this work; Tayama M, Furuhata T, Inafuku Y, Okita K, Nishidate T, Mizuguchi T, Kimura Y and Hirata K designed the research; Tayama M, Furuhata T and Inafuku Y performed the research; Tayama M and Furuhata T provided new reagents/analytic tools; Tayama M, Furuhata T and Okita K analyzed data; and Tayama M, Furuhata T and Hirata K wrote the paper.
Correspondence to: Makoto Tayama, MD, the First Department of Surgery, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. tayama@sapmed.ac.jp
Telephone: +81-11-6112111-3281 Fax: +81-11-6131678
Received: February 5, 2011
Revised: March 28, 2011
Accepted: April 5, 2011
Published online: November 28, 2011
Abstract

AIM: To characterize the implications of vascular endothelial growth factor (VEGF)-A in stromal cells and colorectal cancer and the expression of VEGF-A splice variants.

METHODS: VEGF-A expression in tumor and stromal cells from 165 consecutive patients with colorectal cancer was examined by immunohistochemistry. The association between VEGF-A expression status and clinicopathological factors was investigated. Twenty fresh-frozen samples were obtained for laser capture microdissection to analyze the splice variants of VEGF-A.

RESULTS: VEGF-A was expressed in 53.9% and 42.4% of tumor and stromal cells, respectively. VEGF-A expression in tumor cells (t-VEGF-A) was associated with advanced clinical stage (stage 0, 1/9; stage 1, 2/16; stage 2, 32/55; stage 3, 38/66; stage 4, 16/19, P < 0.0001). VEGF-A expression in stromal cells (s-VEGF-A) increased in the earlier clinical stage (stage 0, 7/9; stage 1, 6/16; stage 2, 33/55; stage 3, 22/66; stage 4, 5/19; P = 0.004). Multivariate analyses for risk factors of recurrence showed that only s-VEGF-A expression was an independent risk factor for recurrence (relative risk 0.309, 95% confidence interval 0.141-0.676, P = 0.0033). The five-year disease-free survival (DFS) rates of t-VEGF-A-positive and -negative cases were 51.4% and 62.9%, respectively. There was no significant difference in t-VEGF-A expression status. The five-year DFS rates of s-VEGF-A-positive and -negative cases were 73.8% and 39.9%, respectively. s-VEGF-A-positive cases had significantly better survival than s-VEGF-A-negative cases (P = 0.0005). Splice variant analysis revealed that t-VEGF-A was mainly composed of VEGF165 and that s-VEGF-A included both VEGF165 and VEGF165b. In cases with no venous invasion (v0), the level of VEGF165b mRNA was significantly higher (v0 204.5 ± 122.7, v1 32.5 ± 36.7, v2 2.1 ± 1.7, P = 0.03). The microvessel density tended to be lower in cases with higher VEGF165b mRNA levels.

CONCLUSION: s-VEGF-A appears be a good prognostic factor for colorectal cancer and includes VEGF165 and VEGF165b.

Keywords: Colorectal cancer, Vascular endothelial growth factor-A, Vascular endothelial growth factor 165, Microvascular density, Stromal cell