子宫颈癌HPV16/18感染与微血管密度和血管内皮生长因子表达的关系

HPV Infection and its Correlation with Microvessel Density and Vascular Endothelial Growth Factor in Human Cervical Carcinoma

目的探讨人乳头状瘤病毒16*18(HPV16*18)在子宫颈癌组织中的感染情况及与微血管密度(MVD)和血管内皮生长因子(VEGF)表达的关系。方法用原位杂交法检测HPV16*18在60例子宫颈癌(鳞癌40例、腺癌20例)、29例宫颈上皮内肿瘤(CIN)和16例正常子宫颈组织中的HPV16*18感染情况;采用免疫组织化学方法(SP)检测VEGF蛋白的表达,并以CD34抗原作为血管内皮细胞标记,测定其微血管密度。结果HPV16*18在子宫颈鳞癌、腺癌、CIN和正常子宫颈组织中感染率分别为67.50%(27*40)、35.00%(7*20)、68.97%(20*29)、6.25%(1*16)。HPV16*18感染率鳞癌组与腺癌组和正常组比较差异均有显著性意义(均P<0.01),而鳞癌组与CIN组相比差异无显著性意义(P>0.05)。随着宫颈病变的进展,MVD逐渐增大,VEGF的阳性表达率渐增高。MVD在以上5种组织间相比差异均有极显著性意义(均P<0.01)。VEGF在子宫颈鳞癌、腺癌、CIN、正常宫颈组织细胞质中的阳性表达率分别为95.00%(38*40)、100.00%(20*20)、82.80%(24*29)、18.80%(3*16)。病变患者与正常者相比差异有极显著性意义(P<0.01)。HPV16*18感染与VEGF表达呈正相关(r=0.245,P<0.05),而与MVD无相关性(r=0.04,P>0.05);VEGF的表达与MVD无相关性(r=0.01,P>0.05)。淋巴转移阳性者MVD的表达量较阴性者高(P<0.05)。结论在子宫颈癌的发生发展中HPV16*18的感染起一定的作用,MVD与VEGF在子宫颈组织的不同病变中的表达均有差异性,推测VEGF有促进子宫颈癌组织血管形成作用,MVD与子宫颈癌的恶性程度密切相关。HPV16*18感染可能通过促进VEGF的表达而有利于子宫颈癌组织的生长。

Objective To investigate infection of human papillomavirus 16/18（HPV16/18）and its correlation with mierovessel density （MVD） and expression of vascular endothelial growth factor （VEGF） in human cervical carcinomas. Methods Tissue specimens were collected from 60 cases of cervical carcinoma （40 squamous cell carcinoma and 20 adenocarcinoma）, 29 cases of cervical intraepithelial neoplasia （CIN） and 16 cases of normal cervices, HPV16/ 18 DNA was detected with in site hybridization method, VEGF and CD34 were stained immunohistoehemieally （SP） and density of mierovessel was assayed. Results The infection rates of HPV16/18 in squamous cell carcinoma, adenoeareinoma, CIN and normal cervical epithelium were 67.5%, 35.0%, 69.0%, 6.3% respectively. There were significant differences when squamous cell carcinoma was compared with adenoeareinoma and the normal cervical epithelium （P〈0.05）, CIN was compared with adenoeareinoma and normal epithelium （P〈0.05）. There were statistically significant differences between adenoeareinoma and the normal epithelium （P〈0.05）, and between glandular and squamous cell carcinoma and normal group （P〈0.01）, but no significant difference between CIN and adenoeareinoma. The MVD and expression rate of VEGF were gradually increased with the progress cervical lesions, There were significant differences among the above 4 groups for MVD （P〈0.01）. The positive rates of VEGF in squamous-eell carcinoma and adenoeareinoma, CIN and in normal cervical epithelium were 95.0%, 100,0% ,82,8%, 18.8% respectively. There were statistically significant differences between these cervical lesion groups and the control group. The infection of HPV16/18 and expression of VEGF was positively correlated （r=0.245 ,P〈0.05） , but not correlated with MVD （r=0.01 ,P〉0.05 ）; and there was no correlation between expression of VEGF and MVD（r=0.04,P〉0.05 ）. There were significant differences inMVD between cases with positive pelvic node metastasis and those with negative pelvic node metastasis （P〈0.05）. No significant correlation was found between the infection of HPV16/18 and expression of VEGF and the tumor diameter, clinical stage, pathologic grade and pelvic node metastasis. Conclusions TThe infection of HPV16/18 may play a role in the progress of carcinoma of the uterine cervix .The expression of MVD and VEGF are significant correlation in different cervical lesions.