Vartanian R K, Weidner N
Department of Pathology, University of California, San Francisco 94143-0102.
Am J Pathol. 1994 Jun;144(6):1188-94.
Tumor angiogenesis is essential for tumor growth and metastasis, and intratumoral microvessel density correlates with prognosis in breast carcinoma. Yet, how intratumoral microvessel density correlates with tumor cell and intratumoral endothelial cell proliferation remains incompletely understood. To this end, we stained 57 formalin-fixed, paraffin-embedded breast carcinomas with antibody MIB1 to determine tumor cell Ki67 labeling index and with anti-CD34 to observe microvessels. We correlated the tumor cell Ki67 labeling index and mitotic figure index with intratumoral microvessel density. Using a double labeling technique combining antibody MIB1 and anti-CD34, we measured intratumoral endothelial cell proliferation in 20 of these cases and correlated these findings with tumor cell Ki67 labeling index, mitotic figure index, and intratumoral microvessel density. The intratumoral Ki67-labeling index was 45-fold greater (P < 0.000001) than that of microvessels in adjacent benign breast. Yet, endothelial cell Ki67 labeling index did not correlate with intratumoral microvessel density, tumor cell Ki67 labeling index, or mitotic figure index nor did intratumoral microvessel density correlate with tumor cell Ki67 labeling index or mitotic figure index. These findings suggest that, although endothelial cells are actively proliferating within the tumor, intratumoral microvessel density and intratumoral endothelial cell proliferation are independent of each other and of tumor cell proliferation. Thus, intratumoral microvessel density, endothelial cell proliferation, and tumor cell proliferation may be regulated by separate mechanisms.
肿瘤血管生成对于肿瘤的生长和转移至关重要，且肿瘤内微血管密度与乳腺癌的预后相关。然而，肿瘤内微血管密度与肿瘤细胞及肿瘤内内皮细胞增殖之间的关系仍未完全明确。为此，我们用MIB1抗体对57例福尔马林固定、石蜡包埋的乳腺癌进行染色，以确定肿瘤细胞的Ki67标记指数，并用抗CD34抗体观察微血管。我们将肿瘤细胞的Ki67标记指数和有丝分裂指数与肿瘤内微血管密度进行关联分析。采用MIB1抗体和抗CD34抗体联合的双重标记技术，我们在其中20例病例中测量了肿瘤内内皮细胞增殖情况，并将这些结果与肿瘤细胞的Ki67标记指数、有丝分裂指数及肿瘤内微血管密度进行关联分析。肿瘤内Ki67标记指数比相邻良性乳腺组织中的微血管Ki67标记指数高45倍（P < 0.000001）。然而，内皮细胞Ki67标记指数与肿瘤内微血管密度、肿瘤细胞Ki67标记指数或有丝分裂指数均无相关性，肿瘤内微血管密度与肿瘤细胞Ki67标记指数或有丝分裂指数也无相关性。这些发现表明，尽管肿瘤内内皮细胞在积极增殖，但肿瘤内微血管密度和肿瘤内内皮细胞增殖相互独立，且与肿瘤细胞增殖无关。因此，肿瘤内微血管密度、内皮细胞增殖和肿瘤细胞增殖可能受不同机制调控。
