Angiogenesis is crucial for tumor growth and metastasis. Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between tumor vascularity and the outcome of patients with HCC has not been evaluated. To clarify whether tumor angiogenesis is related to the prognosis of patients, immunohistochemical staining, using anti-von Willebrand factor (vWF) and anti-CD34, was applied in resected specimens from 43 cases of HCC. In nonmalignant tissue, staining was confined to vessels in the portal tract and to a few periportal sinusoids with both of the endothelial markers applied. In tumor tissue, however, sinusoid-like vessels reacted intensively with anti-CD34 but not with anti-vWF. The intratumor microvessel density (MVD) highlighted by anti-CD34 was 297 +/- 88 (per 0.74 mm2), which was significantly higher than that highlighted by anti-vWF (4 +/- 7). When only the MVD highlighted by anti-CD34 was analyzed, tumor diameter larger than 2 cm, poor differentiation (Edmondson's II to IV), and portal invasion were significantly related to the subgroup with MVD > or = 290. Overall survival curves of patients with MVD < 290 were better, and these patients were more likely to remain tumor free. Cox hazards model revealed intratumor MVD and Edmondson's grade to be independent prognostic factors for the overall survival of patients. These results demonstrated for the first time that tumor angiogenesis assessed by anti-CD34 was correlated with the outcome of patients with HCC, suggesting a potential role for anti-CD34 in the diagnosis and treatment of HCC.
To clarify whether preoperative transcatheter arterial chemoembolization (TAE) improves the prognosis of patients with hepatocellular carcinoma (HCC) after surgery, 120 patients who had undergone hepatectomy for HCC from 1988 to 1994 and satisfied the criteria of stages II and III were enrolled in this study. Forty-four patients underwent preoperative TAE (group A) and 76 patients did not (group B). No significant differences in the outcomes were observed between these two groups. To rectify the comparison, patients with tumors 2 to 8 cm were assigned to groups A1 (n = 24) and B1 (n = 57), and those with tumors > 8 cm were assigned to groups A2 (n = 20) and B2 (n = 19), respectively. Although no significant differences in survival between groups A1 and B1 were found, group A2 presented superior 1-, 2-, and 3-year tumor-free survival rates of 80%, 55%, and 32% and 1-, 3-, and 5-year cumulative survival rates of 90%, 53%, and 42%. These figures are in comparison with the tumor-free survival rates of 50%, 22%, and 11% (p = 0.06), and the cumulative survival rates of 72%, 33%, and 11% (p = 0.01) during the same periods for group B2, respectively. The Cox regression model revealed that for patients with tumors > 8 cm, the relative risk of preoperative TAE for overall survival was 0.38 (p = 0.017), indicating that preoperative TAE might benefit patients with tumors > 8 cm but not those with tumors 2 to 8 cm.
These findings support the hypothesis that tumor angiogenesis is closely related to the overall survival of patients with esophageal squamous cell carcinoma. The extent of tumor vascularity may serve as a reliable prognostic marker with which patients at risk for recurrence can be identified.
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