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Purpose: Expression of angiogenetic factors and receptors in various kinds of cancer tissue and their clinical significance have been reported, but there have been a few reports on esophageal cancer except in regard to VEGF. Expression of Flt-1 and KDR/Flk-1, which are the receptors of VEGF, and expression of acidic FGF (aFGF), basic FGF (bFGF) and their receptor FGFR-1 were examined and clarified in esophageal cancer tissues. Materials and Methods: Seventy-nine cases resected in the Department of Surgery, Keio University Hospital between 1990 to 1993, were studied in this subject. All cases were pathologically diagnosed as squamous cell carcinoma. These patients were previously untreated. Formalin-fixed and paraffin-embedded sections of esophageal cancer tissues were stained by immunohistochemical methods and examined for expression of angiogenetic factors, their receptors, and microvascular. We examined relations between expression of the angiogenetic factors and their receptors, and relations among each of them and tumor depth, lymphatic invasion, venous invasion, intraepidermal expansion, intramural metastasis, lymph node metastasis, clinical stage, microvascular density (MVD), tumor area, number of metastatic lymph node and survival time. Data were statistically compared by the chi-square test, Mann Whitney’s U test, and the logrank test for a survival analysis. Results: The Flt-1 positive group had a greater depth of tumor invasion (p=0.007), more lymphatic invasion (p=0.008) and more lymph node metastasis (p=0.01) than the negative group. The aFGF positive group had a larger tumor area than the negative group (p=0.009). Both aFGF and bFGF positive group had more lymph node metastasis than both negative group (p=0.03). All of VEGF, Flt-1 and KDR/Flk-1 positive group tended to have a shorter survival time than the negative group (p=0.10). Both aFGF and FGFR-1 positive group had a shorter survival time than both negative group (p=0.04). A positive correlation was found between expression of aFGF and FGFR-1 (p<0.0001), and between expression of bFGF and FGFR-1 (p=0.04). Conclusions: Expression of VEGF and its receptors, aFGF, bFGF and their receptors correlate with the development of esophageal cancer tissue and prognosis. Positive correlation between expression of aFGF and FGFR-1 and between expression of bFGF and FGFR-1 suggest the presence of the autocrine / paracrine mechanism that promotes the development of cancer cells.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]