子宫颈腺癌中HPV16/18感染对p16Ink4a、Rb蛋白表达的影响

目的研究16、18型人乳头瘤病毒(HPV16/18)DNA与细胞周期相关蛋白p16Ink4a、Rb在子宫颈腺癌中的表达情况及HPV16/18感染对p16Ink4a、Rb蛋白表达的影响。方法采用组织微阵列技术结合原位杂交和免疫组化EliVision二步法标记检测HPV16/18DNA和p16Ink4a、Rb蛋白在86例子宫颈腺癌、15例子宫颈腺上皮异型增生及24例慢性子宫颈炎组织中的表达。结果子宫颈腺癌组和子宫颈腺上皮异型增生组HPV16/18DNA阳性表达率分别为65·1%和46·7%,均明显高于慢性子宫颈炎组8·3%(P<0·01);p16Ink4a蛋白在子宫颈腺癌组的阳性表达率为74·4%,显著高于慢性子宫颈炎组33·4%(P<0·01)。Rb蛋白在子宫颈腺癌组的阳性表达率为33·7%,低于慢性子宫颈炎组45·8%,但差异无显著性(P>0·05)。HPV16/18感染与子宫颈腺癌的病理分级和组织学类型无关,但与p16Ink4a蛋白表达呈正相关(P<0·05)。p16Ink4a与Rb蛋白表达与子宫颈腺癌的病理分级有关,G2、G3组p16Ink4a阳性表达率明显高于G1组(P<0·05),G3组Rb阳性表达率明显低于G1组(P<0·05)。p16Ink4a表达与子宫颈腺癌组织学类型有明显相关性,子宫内膜样腺癌p16Ink4a阳性表达率明显高于透明细胞腺癌(P<0·05)。结论子宫颈腺癌的发生与HPV16/18感染有关,HPV16/18感染可能影响p16Ink4a、Rb蛋白表达,使子宫颈腺上皮发生癌变并促进恶性发展。

Influence of HPV16/18 infection on expressions of p16Ink4a and Rb proteins in adenocarcinoma of cervix

Purpose To study the expression of human papilloma viruses 16 and 18 (HPV16/18) DNA and the cell cycle proteins of p16~ Ink4a and Rb in cervical adenocarcinoma and the influence of HPV16/18 infection on expressions of p16~ Ink4a and Rb protein. Methods The expressions of HPV16/18DNA and p16~ Ink4a and Rb proteins were determined by tissue microarray combined with in situ hybridization and immunohistochemistry in 86 cases of cervical adenocarcinoma,15 cases of endocervical glandular dysplasia and 24 cases of cervical chronic inflammation. Results The positive rates of HPV16/18 DNA in cervical adenocarcinoma and glandular dysplasia were 65.1% and 46.7% respectively, which significantly higher than that in cervical chronic inflammation (8.3%, P<0.01); The positive rate of p16~ Ink4a protein in cervical adenocarcinoma was 74.4%, which was significantly higher than that in cervical chronic inflammation (33.4%, P<0.01); The positive rate of Rb protein in cervical adenocarcinoma was 33.7%, which was slightly lower than that in cervical chronic inflammation (45.8%), but without statistic significance (P>0.05). There was no relationship between HPV16/18 infection and the pathological grades or histological subtypes. However, there was positive correlation between HPV16/18 infection and p16~ Ink4a protein expression (P<0.05) . The expressions of p16~ Ink4a and Rb proteins were also related to the pathological grades. The positive rate of p16~ Ink4a was significantly higher in G_2 and G_3 than that in G_1(P<0.05), and that of Rb was significantly lower in G_3 than in G_1 (P<0.05). The expression of p16~ Ink4a was related to the histological types, and the levels of p16~ Ink4a were significantly higher in endometrioid adenocarcinoma than in clear cell adenocarcinoma (P<0.05). Conclusions The pathogenesis of cervical adenocarcinoma may be related to the infection of HPV16/18, which may influence the expressions of p16~ Ink4a and Rb proteins, induce the occurrence of the cervical adenocarcinoma and might play an important role in the development of the adenocarcinoma.