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  

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

作　　者：俞岚[1,2] 武世伍[1,2] 周蕾[1,2] 宋文庆[1,2] 

机构地区：[1]蚌埠医学院第一附属医院病理科 [2]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

出　　处：《生理学报》2012年第6期657-665,共9页Acta Physiologica Sinica

基　　金：supported by the Science Foundation for Young Talents in Universities of Anhui Province;China (No.2012SQRL094)

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。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 wasalso 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, clinic

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 

分 类 号：R737.31[医药卫生—肿瘤]