目的 探讨Ⅳ型胶原和基质金属蛋白酶-2(MMP2)、MMP9在胆囊癌血管生成拟态(VM)中的表达与意义。方法 74例胆囊癌、胆囊腺瘤和慢性胆囊炎各10例病理标本及资料,应用免疫组织化学Envision、SABC法测定上述病变组织Ⅳ型胶原和MMP2、MMP9表达,Kaplan-Meier生存曲线和Cox风险模型分析其与胆囊癌VM的相关性和临床意义。结果 (1)在VM(+)胆囊癌,Ⅳ型胶原表达明显低于、MMP2表达明显高于VM(-)胆囊癌(P〉0.01),MMP9则无差异。(2)Ⅳ型胶原与VM(+)胆囊癌分化程度负相关;MMP2、MMP9与VM(+)胆囊癌的Nevin晚期、侵犯浆膜、肝转移正相关,MMP2尚与VM(+)胆囊癌的低分化和淋巴结转移正相关。(3)Ⅳ型胶原阳性和MMP2、MMP9阴性VM(+)胆囊癌患者术后5年生存期明显短于VM(-)胆囊癌(P〈0.01;P〈0.05;P〈0.01),MMP2阳性VM(+)胆囊癌患者术后5年生存期亦明显短于VM(-)胆囊癌。VM、1V型胶原是影响胆囊癌患者预后的独立因素。结论Ⅳ型胶原、MMP2分别与胆囊癌VM呈负、正相关,MMP9与胆囊癌VM无关;Ⅳ型胶原和MMP2可作为判断胆囊癌是否存在VM及VM胆囊癌预后的重要指标。
Objective To investigate the expression of collagen Ⅳ and matrix metalloproteinase- 2 (MMP2) ,-9(MMP9) in human primary gallbladder carcinomas with vasculogenic mimicry (VM) and its significance. Methods Seventy-four carcinomas, 10 adenomas and 10 chronic inflammatory lesions of the gallbladder confirmed histopathologically and their clinical-pathlogical data were studied and followedup. Envision method and streptavidin-biotin complex method of immunohistochemistry were used to determine the expression of collagen Ⅳ, MMP2 and MMP9 proteins in each paraffin section of every patient in vivo. Kaplan-Meier actuarial survival curves and Cox multiple factors were used to analyze the correlation among the expression of collagen Ⅳ ,MMP2 and MMP9 proteins and the gallbladder carcinomas with VM, and clinical significance. Results ( 1 ) Expression of collagen Ⅳ in the gallbladder carcinomas with VM was decreased significantly than that of the gallbladder carcinomas without VM (P 〉 0.01 ). Moreover,expression of MMP2 in the gallbladder carcinomas with VM was increased significantly than that without VM (P 〉 0.01 ) ,without difference on expression of MMP-9 between the gallbladder carcinomas with VM and those without VM. (2)There is negative correlation between expression of collagen Ⅳ and the gallbladder carcinomas with VM in the cases of differentiation degree ; The positive correlation was observed between expression of MMP2 or MMP9 and the gallbladder carcinomas with VM in the cases of Nevin stage,inva- sion depth and liver metastasis, with positive correlation between expression of MMP2 and the gallbladder carcinomas with VM in the cases of differentiation degree and lymph node metastases. ( 3 ) The non-VM group with positive expression of collagen Ⅳ, negative expression of MMP2 and MMP9 had more longer 5- year survival rates than the respectively VM group (P 〈0.01 ,P 〈0.05 ) ; The VM group with negative expression of MMP2 had lower 5-year survival rate than the non