宫颈癌及宫颈上皮内瘤样病变组织中端粒酶的活性及其与凹空细胞分型的关系

Telomerase activity in cervical carcinoma and cervical intraepithelial neoplasia and its correlation to classification of koilocytosis

目的 研究宫颈上皮内瘤样病变 (CIN)及宫颈癌的组织和脱落细胞中端粒酶的活性变化 ,探索端粒酶激活与凹空细胞分型及人乳头状瘤病毒 (HPV)感染之间的关系。方法 采用端粒酶重复扩增技术 (TRAP) ,检测 2 4例正常宫颈、34例宫颈炎症、78例CIN及 16例宫颈癌的宫颈组织和脱落细胞中端粒酶的活性。同时采用双盲法检测上述宫颈病变组织中凹空细胞的分布 ,并将其分为Ⅰ型和Ⅱ型。结果 组织中端粒酶阳性率分别为 :正常宫颈组织为 16 7% (4/ 2 4 ) ,炎症组织为 17 6 %(6 / 34) ,CIN1组织为 5 1 6 % (16 / 31) ,CIN2 组织为 72 0 % (18/ 2 5 ) ,CIN3 组织为 86 4 % (19/ 2 2 ) ,宫颈癌组织为 10 0 % (16 / 16 )。端粒酶阳性率CIN明显高于正常宫颈及炎症组织 (P <0 0 1) ;宫颈癌组织明显高于CIN组织 (P <0 0 5 ) ;CIN3 高于CIN1(P <0 0 5 ) ;而正常宫颈与炎症组织比 ,CIN1与CIN2 比 ,CIN2 与CIN3 比较 ,差异均无显著意义 (P >0 0 5 )。相应的宫颈脱落细胞中端粒酶阳性率同组织标本比 ,差异无显著意义 (P >0 0 5 )。含Ⅰ型、Ⅱ型凹空细胞的宫颈病变组织中端粒酶阳性率分别为 6 6 7%和10 0 % ,两者差异有显著意义 (P <0 0 1)。结论 (1)端粒酶的激活与宫颈癌及CIN的发展有密切关系 。

Objective To investigate the telomerase activity in cervical tissues and exfoliated cells in patients with cervical intraepithelial neoplasia(CIN)and cervical carcinoma, and to study the correlation between telomerase activativity and koilocytotisis classification and between telomorase activity and human papillomavirus(HPV)infection. Methods Telomeric repeat amplification protocol (TRAP)was used to determine the telomerase activity in cervical tissues and exfoliated cells in 24 women with normal cervix,34 patients with cervitis,78 patients with CIN and 16 patients with cervical carcinoma. The patients with CIN were classified into 3 subgroups according to the abnormality of cervical cells (31 CIN 1 cases,25 CIN 2 cases and 22 CIN 3 cases). The presence and classification of koilocyte in cervical tissues was examined by microscopy with double blind method. The telomerase activity in koilocytes of different types was investigated. Results The telomerase positive rate was 16 7%(4/24) in normal cervical tissue,17 6%(6/34) in cervitis tissue,51 6%(16/31) in CIN 1 tissue ,72 0%(18/25) in CIN 2 tissue ,86 4%(19/22) in CIN 3 tissue, and 100%(16/16) in cervical carcinoma tissue respectively. The telomerase positive rate in CIN cases was significantly higher than those in normal cervix and cervitis cases(all P <0 01) and the telomerase positive rate was significantly higher in cervical carcinoma than in CIN( P <0 01). It was also significantly higher in CIN 3 than in CIN 1( P <0 05),while no significant difference was found in the telomerase positive rate between normal cervix and cervitis,CIN 1 and CIN 2,and CIN 2 and CIN 3( P >0 05). No significant difference of telomerase positive rate was found between the cervical tissue and exfoliated cells in the same case too( P >0 05). Koilocytes were found in sixty four out of the 154 samples of cervical lesions. Among them koilocytes were found in 54 out of 94 samples of cervical cancer and CIN tissues (koilocytes of type I in 18 cases and type II in 36 cases). The telomerase positive rate was 100% in tissues of CIN and cervical carcinoma with type Ⅱ koilocytosis, significantly higher than that in tissues with type Ⅰkoilocytosis (66 7%, P <0 05). Conclusion (1)Activation of telomerase is closely associated with progression of CIN and cervical carcinoma,and telomerase might be a useful marker for cervical carcinoma and CIN. (2)Cervical exfoliated cells may be used as the substitute of cervical tissues in determining telomerase activity. (3)Activation of telomerase is correlated with type Ⅱ koilocytosis and HPV 16/18 infection.