宫颈癌与HPV16 E6及hWAPL的相关性研究

摘要

目的：检测宫颈不同级别病变组织中人乳头瘤病毒16 E6（HPV16 E6）及人半翼基因（hWAPL）的表达，分析宫颈癌与HPV16 E6及hWAPL蛋白的相关性，为早期诊断宫颈癌提供依据。方法采用免疫组化方法检测宫颈不同级别病变组织的石蜡包埋块，其中宫颈上皮细胞内瘤变（CIN）Ⅰ或CIN Ⅱ49例，CIN Ⅲ或原位癌33例，宫颈浸润癌（ICC）28例，正常宫颈上皮组织16例。结果 HPV16E6与hWAPL在正常宫颈组、CINⅠ或Ⅱ组、CINⅢ组和ICC组的组织中阳性表达率呈逐渐增高趋势，HPV16E6与hWAPL在CINⅢ组和ICC组的阳性表达率与正常宫颈组、CINⅠ或Ⅱ组差异有统计学意义（P＜0．05）。CINⅢ组和ICC组HPV16E6蛋白阳性表达率差异有统计学意义（P＜0．05），而hWAPL蛋白的阳性表达率无明显差异（P＝0．372）。HPV16E6与hWAPL的表达强度在ICC组、CINⅢ组明显高于CINⅠ或Ⅱ组和正常宫颈组（P＜0．05），而ICC组与CINⅢ组之间无明显差异（P＞0．05）。64例HPV16E6阳性者中57例（89．06％）hWAPL蛋白表达阳性，62例阴性者中15例（24．19％）hWAPL蛋白表达阳性。经统计学处理，二者有明显相关性（P＜0．05），而且HPV16E6感染强度与hWAPL表达呈正相关（r＝0．595， P＜0．001）。结论 hWAPL基因是宫颈癌特异性高表达基因，具有癌基因特性，可能是宫颈癌发生机制中的重要环节，而且可能成为新的检测指标，用于宫颈鳞癌的基因诊断、治疗及明确病变程度。%Objective To investigate the expressions of human papillomavirus 1 6E6 (HPV1 6 E6 )and human wings apart-like gene (hWAPL)in different levels of cervical lesions and the relationship of HPV1 6E6 and hWAPL protein with cervical cancer,and to provide the reference for the early diagnosis of cervical cancer.Methods By immunohistochemistry,the paraffin-embedded blocks with different levels of cervical lesions were detected,including 49 patients with cervical intraepitelial neoplasia (CIN)Ⅰ or CIN Ⅱ,33 patients with CIN Ⅲ or carcinoma in situ,28 patients with invasive cervical carcinoma (ICC)and 1 6 patients with normal cervical epithelium.Results In normal, CIN Ⅰ or Ⅱ,CIN Ⅲ and ICC groups,the positive expression rates of HPV1 6E6 and hWAPL showed gradually increasing trend.The positive expression rates of HPV1 6E6 and hWAPL in CIN Ⅲ and ICC groups had statistical significance with those in normal and CIN Ⅰ or CIN Ⅱ groups (P<0.05 ).Between CIN Ⅲ and ICC groups,the positive expression rate of HPV1 6E6 had statistical significance (P<0.05),but the positive expression rate of hWAPL protein had no obvious difference (P=0.372).HPV1 6E6 and hWAPL expression strengthes in ICC group and CIN Ⅲgroup were obviously higher than those in CIN Ⅰ orⅡgroup and normal group (P<0.05),and there was no obvious difference between ICC and CIN Ⅲ groups (P>0.05 ).The 57 of 64 patients (89.06%)with HPV1 6E6 had the positive expression of hWAPL protein,1 5 of 62 patients (24.1 9%)with no HPV1 6E6 had the positive expression of hWAPL protein.By statistical analysis,both HPV1 6E6 and hWAPL protein had significant correlation (P<0.05),and it showed that the infection intensity of HPV1 6E6 and the expression of hWAPL had positive correlation (r=0.595,P<0.001 ).Conclusions The hWAPL may be a cervical cancer-specific gene and expresses highly,and it may be important in the pathogenesis of cervical cancer.The hWAPL may become the new target gene for the diagnosis, treatment and lesion identification of cervical cancer.