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Biopsy Specimen Microvessel Density Is a Useful Prognostic Marker in Patients with T_2–4M₀ Esophageal Cancer Treated with Chemoradiotherapy¹

Pathology Division, National Cancer Center Research Institute East, Chiba 277-8577, Japan [S. H., T. H., T. K., A. Oc.]; Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba 277-8577, Japan [S. H., A. Oh., N. B., S. Y.]; and Second Department of Internal Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan [H. S.]

Purpose: The purpose of this study was to identify prognostic markers for chemoradiotherapy (CRT) in T_2–4M₀ esophageal cancer.

Experimental Design: We investigated clinicopathological and biological markers in biopsy specimens from 73 T_2–4M₀ esophageal cancer patients treated with CRT (5-fluorouracil plus cisplatin and 60 Gy of radiation). Expressions of p53 gene product, Ki-67 labeling index, epidermal growth factor receptor, cyclin D1, vascular endothelial growth factor, microvessel density (MVD), thymidylate synthase, dihydropyrimidine dehydrogenase, and glutathione S-transferase in formalin-fixed biopsy samples of primary tumors before CRT were examined immunohistochemically. Clinicopathological and biological marker expressions were compared in terms of survival.

Results: Univariate analysis revealed that performance status and T stage in clinicopathological features had a significant association with survival (P = 0.007 and 0.04, respectively) and that patients whose tumors showed high MVD [>median (19.7 vessels)] in biological markers had significantly better survival than those with low MVD (median, P = 0.02). Also, there were weak associations of p53 and Ki-67 with survival (P = 0.08 and 0.07, respectively). Multivariate analysis, using both clinicopathological and biological markers, showed that MVD, T stage, and performance status became independent variables (P = 0.002, 0.02, and 0.02, respectively). Kaplan-Meier analysis showed that the patients with high MVD tumors survived longer than those with low MVD tumors (median survival time, not reached and 13 months, respectively; 3-year survival rate, 61% and 33%, respectively), with a significant difference of P = 0.02.

Conclusions: These results indicate that MVD using pretreatment biopsy specimens is a potentially useful prognostic marker for CRT in patients with T_2–4M₀ esophageal cancer who are treated with CRT.

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