Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T, Horiuchi T, Muraoka R, Iki M
The Second Department of Surgery, Fukui Medical School, Japan.
Cancer Res. 1996 Jun 1;56(11):2671-6.
To determine whether tumor angiogenesis correlates with prognosis and metastasis of patients with gastric carcinoma, we counted the microvessels within the primary carcinoma and compared their numbers with the patient's prognosis and mode of metastasis. Tumor specimens from 110 patients with gastric carcinoma, who had undergone curative resection more than 24 months before, were investigated. Intratumoral microvessels were stained with anti-CD34 and anti-von Willebrand factor monoclonal antibodies before being quantitated by light microscopy (x200). The antibody against von Willebrand factor often showed variability and stromal background staining, providing misleading low vessel counts. The data from three patients who died from nongastric carcinoma within 24 months after surgery were deleted. A total of 107 patients took part in the analysis examining the association between intratumoral microvessels and clinical outcomes. Vessel counts derived from CD34 expression were significantly higher in patients who experienced hematogenous or peritoneal metastasis after surgery than in patients with nonmetastatic tumors. No correlation between vessel counts and lymph node metastasis was found. The prevalence of hematogenous metastasis. but not peritoneal metastasis, increased as the vessel counts increased. Multivariate logistic regression and Cox hazards model analyses showed that the vessel counts obtained with CD34 staining correlated with the development of hematogenous recurrence but not peritoneal recurrence. It was the most important factor for predicting overall survival. These findings support the hypothesis that tumor angiogenesis is closely related to the development of hematogenous metastasis in human gastric carcinomas. Assessment of tumor vascularization may, therefore, prove valuable in identifying patients with gastric carcinoma at high risk for recurrence who would benefit from adjuvant therapy.
为了确定肿瘤血管生成是否与胃癌患者的预后及转移相关,我们对原发性癌组织内的微血管进行计数,并将其数量与患者的预后及转移方式进行比较。研究了110例胃癌患者的肿瘤标本,这些患者均在24个月前接受了根治性切除术。肿瘤内微血管先用抗CD34和抗血管性血友病因子单克隆抗体染色,然后通过光学显微镜(×200)进行定量。抗血管性血友病因子抗体常出现变异及基质背景染色,导致血管计数偏低而产生误导。剔除了3例术后24个月内死于非胃癌的患者的数据。共有107例患者参与了肿瘤内微血管与临床结局之间相关性的分析。术后发生血行转移或腹膜转移患者的CD34表达所衍生的血管计数显著高于无转移肿瘤患者。未发现血管计数与淋巴结转移之间存在相关性。随着血管计数增加,血行转移的发生率升高,但腹膜转移并非如此。多因素logistic回归分析和Cox风险模型分析显示,CD34染色获得的血管计数与血行复发的发生相关,但与腹膜复发无关。它是预测总生存的最重要因素。这些发现支持肿瘤血管生成与人类胃癌血行转移的发生密切相关这一假说。因此,评估肿瘤血管化可能对识别复发高危的胃癌患者有价值,这些患者可能从辅助治疗中获益。