Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis - PubMed (original) (raw)

Comparative Study

Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis

Tatsuya Tanaka et al. J Exp Clin Cancer Res. 2010.

Abstract

Background: The diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings.

Methods: KYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR.

Results: High expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026). The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0-2A tumors (p = 0.049). When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression), the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065). Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029). The survival rate of patients from the high expression group (n = 10) was lower than that in the low expression group (n = 11), and all the patients in the low VEGF-C expression group survived.

Conclusions: The expression of VEGF-C correlates with lymph node metastasis and poor prognosis. In patients with Tis and T1 esophageal tumors, the expression of VEGF-C may be a good diagnostic factor for determining metastasis of the lymph node.

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Figures

Figure 1

Figure 1

The expression of VEGF-C in esophageal cell lines. Most KYSE cell lines express VEGF-C. Het-1A cells do not express VEGF-C.

Figure 2

Figure 2

Comparison of mRNA expression of VEGF-C in cancer and corresponding noncancerous esophageal mucosa (a) and in Stage0-2A patients and Stage2B-4A patients (b). The VEGF-C expression in ESCC tumors is significantly higher than in the corresponding noncancerous esophageal mucosa (a). The VEGF-C expression is higher in Stage2B-4A patients than in Stage0-2A patients (b).

Figure 3

Figure 3

Survival rate of patients with ESCC according to the mRNA expression of VEGF-C. Patients with high expression of VEGF-C have significantly shorter survival after surgery (p = 0.0065 by log-rank test). The cut off value was median expression of VEGF-C

Figure 4

Figure 4

The mRNA expression of VEGF-C in Tis and T1 ESCC tumors. The expression of VEGF-C is higher in N1 tumors than in N0 tumors (p = 0.029).

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References

    1. Maesawa C, Tamura G, Suzuki Y, Ogasawara S, Ishida K, Saito K, Satodate R. Aberrations of tumor-suppressor genes (p53, apc, mcc and Rb) in esophageal squamous-cell carcinoma. Int J Cancer. 1994;57:21–25. doi: 10.1002/ijc.2910570105. - DOI - PubMed
    1. Dolan K, Garde J, Walker SJ, Sutton R, Gosney J, Field JK. LOH at the sites of the DCC, APC, and TP53 tumor suppressor genes occurs in Barrett's metaplasia and dysplasia adjacent to adenocarcinoma of the esophagus. Hum Pathol. 1999;30:1508–1514. doi: 10.1016/S0046-8177(99)90175-2. - DOI - PubMed
    1. Nishiwaki T, Daigo Y, Kawasoe T, Nakamura Y. Isolation and mutational analysis of a novel human cDNA, DEC1 (deleted in esophageal cancer 1), derived from the tumor suppressor locus in 9q32. Genes Chromosomes Cancer. 2000;27:169–176. doi: 10.1002/(SICI)1098-2264(200002)27:2<169::AID-GCC8>3.0.CO;2-M. - DOI - PubMed
    1. Miyake S, Nagai K, Yoshino K, Oto M, Endo M, Yuasa Y. Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis. Cancer Res. 1994;54:3007–3010. - PubMed
    1. Daigo Y, Nishiwaki T, Kawasoe T, Tamari M, Tsuchiya E, Nakamura Y. Molecular cloning of a candidate tumor suppressor gene, DLC1, from chromosome 3p21.3. Cancer Res. 1999;59:1966–1972. - PubMed

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