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细菌L型感染、低氧诱导因子-1α及MMP-9表达与卵巢上皮性癌血管生成拟态的关系

俞岚^*, 武世伍, 周蕾, 宋文庆

蚌埠医学院第一附属医院病理科，蚌埠医学院病理学教研室，安徽省感染与免疫重点实验室，蚌埠 233030

摘要

本文旨在探讨血管生成拟态(vasculogenic mimicry, VM)与细菌L型(L-form)感染、低氧诱导因子-1α (hypoxia inducible factor 1α, HIF-1α)及MMP-9 (matrix metalloproteinase-9)在人卵巢上皮性癌(epithelial ovarian cancer, EOC)组织中表达的关系及功能意义。收集87例EOC术后标本和20例卵巢良性上皮性肿瘤标本，应用免疫组化法、组织化学及革兰染色法检测EOC和卵巢良性上皮性肿瘤组织中VM、HIF-1α、MMP-9的表达及细菌L型的感染情况。结果显示，在EOC和卵巢良性上皮性肿瘤组织中，HIF-1α和MMP-9的阳性表达率分别为52.9%、66.7%和10.0%、10.0%；细菌L型的感染率分别为24.1%和0，差异均有统计学意义(P < 0.01)；细菌L型的感染与EOC的临床FIGO分期、腹腔种植及淋巴结转移有关(P < 0.01或0.05)， HIF-1α、MMP-9的表达与EOC的组织学分级、腹腔种植、淋巴结转移以及FIGO分期有关(P < 0.01)；HIF-1α的表达分别与VM的形成及MMP-9的表达呈正相关(r值分别为0.585和0.505，均P < 0.01)，同时，MMP-9的表达与VM的形成亦呈正相关(r = 0.625，P < 0.01)。Kaplan-Meier生存分析表明，VM、HIF-1α及MMP-9的过表达均与患者的生存率有关，阳性表达的患者生存率明显低于阴性者(P < 0.05)；有细菌L型感染的EOC患者生存率亦明显低于未感染者(P < 0.05)。多因素分析表明FIGO分期、VM、HIF-1α及MMP-9的表达是影响EOC根治术后患者预后的独立因素(P < 0.05)。以上结果提示，EOC组织中细菌L型感染、HIF-1α和MMP-9的过表达以及VM的形成与肿瘤的分化程度、转移和预后等因素均有关，这些指标的联合检测可能对EOC的进展及预后判断有着重要意义。

关键词： 卵巢上皮性癌; 血管生成拟态; 低氧诱导因子-1α; 基质金属蛋白酶-9; 细菌L型; 预后

[Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer.] [Article in Chinese]

YU Lan^*, WU Shi-Wu, ZHOU Lei, SONG Wen-Qing

Department of Pathology, the first Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Anhui Key Laboratory of Infection and Immunology, Bengbu 233030, China

Abstract

The aim of the present study is to explore whether vasculogenic mimicry (VM) and bacterial L-form infection exist in human epithelial ovarian cancer (EOC) or not and to elucidate the correlation of L-form infection, expression of hypoxia inducible factor 1α (HIF-1α)/MMP-9 and VM. In 87 specimens of EOC and 20 specimens of ovarian benign epithelial tumor tissues, L-form infection was detected by Gram’s staining, expression of HIF-1α/MMP-9 and VM were detected by immunohistochemical and histochemical staining. The results showed that the positive rates of HIF-1α and MMP-9 protein in EOC were 52.9% and 66.7%, while in benign epithelial tumor tissues, the positive rates were 10.0% and 10.0% respectively, and there were significant differences between them (P < 0.05). In EOC and benign epithelial tumor tissues, L-form infections ratios were 24.1% and 0, respectively, and the difference was also significant (P < 0.01). Expression of VM, HIF-1α and MMP-9 in EOC was significantly related to differentiation, abdominal implantation and lymph node metastasis and FIGO stage (P < 0.01). L-form infection had relationship with abdominal implantation, lymph node metastasis and FIGO stage (P < 0.01 or 0.05). The expression of HIF-1α had positive relationship with expression of MMP-9 and VM (r = 0.505, 0.585, respectively, P < 0.01); there was also a positive relationship between MMP-9 expression and VM (r = 0.625, P < 0.01). Overexpression of VM, HIF-1α and MMP-9 were related to poor prognosis: the survival rates were significantly lower in positive patients than those in negative patients (P < 0.05). And the group with L-form infection also had poor prognosis: the survival rates were lower than those in group without infection (P < 0.05). FIGO stage, expression of VM, HIF-1α and MMP-9 were independent prognosis factors of EOC (P < 0.05). The results suggest that L-form infection, the expression of HIF-1α, MMP-9 and VM in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes has an important role in predicting the progression and prognosis of EOC.

Key words: epithelial ovarian cancer; vasculogenic mimicry; HIF-1α; MMP-9; L-form; prognosis

收稿日期：2012-01-15　　录用日期：2012-04-20

通讯作者：俞岚　　E-mail: yulan790210@163.com

引用本文：

俞岚, 武世伍, 周蕾, 宋文庆. 细菌L型感染、低氧诱导因子-1α及MMP-9表达与卵巢上皮性癌血管生成拟态的关系[J]. 生理学报 2012; 64 (6): 657-665.

YU Lan, WU Shi-Wu, ZHOU Lei, SONG Wen-Qing. [Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer.] [Article in Chinese] . Acta Physiol Sin 2012; 64 (6): 657-665 (in Chinese with English abstract).