宫颈脱落细胞中hTERC基因扩增及其临床意义
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摘要
目的:探讨宫颈上皮内瘤变(CIN)、宫颈癌患者人端粒酶RNA(hTERC)基因扩增及其临床意义。方法:收集2008年2月～2009年2月新疆医科大学附属肿瘤医院120例宫颈脱落细胞标本,应用荧光原位杂交技术(FISH)检测hTERC基因扩增情况和基因芯片导流杂交技术检测HPVDNA感染情况。结果:(1)在细胞学分组中正常细胞组、无明确诊断意义的不典型鳞状细胞(ASCUS)组、低度鳞状上皮细胞内病变(LSIL)组、高度鳞状上皮细胞内病变(HSIL)组、鳞状细胞癌(SCC)组患者宫颈脱落细胞中hTERC基因扩增的阳性率分别是0%、11.1%、33.3%、77.8%、100%,hTERC基因扩增的阳性率差异有统计学意义(P<0.05);通过调整检验水准(α=0.005)后,进行组间两两比较,差异有统计学意义。(2)在组织病理学分组中宫颈上皮内瘤变Ⅰ级(CINⅠ)组、宫颈上皮内瘤变Ⅱ/Ⅲ级(CINⅡ/Ⅲ)组和宫颈鳞状细胞癌(SCC)组患者宫颈脱落细胞中hTERC基因扩增的阳性率分别是30.0%、67.5%和92.5%,hTERC基因扩增的阳性率差异有统计学意义(P<0.05);通过调整检验水准(α=0.017),进行组间两两比较,差异有统计学意义。(3)正常宫颈脱落细胞hTERC基因的表达类型是2:2型,CIN、SCC组hTERC基因表达类型以2:3、2:4、2:5、3:3、2:6、4:4为主,在SCC组中拷贝数亦在增加。(4)汉族、维吾尔族CIN患者hTERC基因扩增阳性率分别42.9%和52.0%,两组之间差异无统计学意义(P>0.05)。(5)汉族、维吾尔族SCC患者hTERC扩增阳性率分别是87.5%和95.6%,两组之间差异无统计学意义(P>0.05 )。(6)CIN组和SCC组患者宫颈脱落细胞中hTERC基因异常扩增和HPV感染之间存在关联性(r=0.814,P=0.001)。结论:hTERC基因在宫颈上皮内瘤变和宫颈鳞状细胞癌中异常扩增,且随病变程度增加而增加,扩增的倍数亦增加,从宫颈癌筛查及早期诊断的角度出发,可作为宫颈病变进展的生物学监测指标;hTERC基因扩增在汉族、维吾尔族CIN及SCC患者中无民族差异性;在宫颈上皮内瘤变和鳞状细胞癌中hTERC基因异常扩增和HPV感染关系密切。
Objective: To investigate the clinical significance and amplification of the human telomerase compenent (hTERC) gene in the cytologic specimens of cervix. Methods: The fluorescence signal of 120 cases cytologic samples of cervix were detected by using Interphase FISH in chromosome enumeration double-color DNA probes TERC. 60 cases of cervical intraepithelial neoplasia and 40 cases of squamous cell carcinomas were determined for HPVDNA by the channelization hybridization genechip. Results: (1) in cytological examination: the amplication rates of hTERC in the normal sample were 0%, while 11.1% of the atypical squamous cell of unde-termined significance, 33.3% of the low-grade squamous intraepithelial, 77.8% of the high-grade squamous intraepithelial and 100% of the squamous cell carcinoma showed that extra copies of 3q.TERC copy numbers in HSIL and SCC were significantly higher than that in normal cell, ASCUS and LSIL, and the overall amplification rates of hTERC among groups have statistically significant(P<0.05). (2) in histology biopsy: the amplication rates of hTERC in the cervical intraepithelial neoplasiaⅠlesions were 30%, while 67.5% of the cervical intraepithelial neoplasiaⅡ/Ⅲlesions and 92.5% of the squamous cervical cancer showed that extra copies of 3q. TERC copy numbers in CINⅡ/Ⅲwere significantly higher than that in CINⅠ. The percentage of multiple 3q signals increased with the severity of the cytologic interpretation, the differences were statistically significant (P<0.05). (3) we observed the types of 3q. TERC copy numbers in the cytologic specimens of cervix of normal sample were 2:2, the types of 3q. TERC copy numbers were 2:3、2:4、2:5、3:3、2:6、4:4 in the CIN and SCC. (4) The amplification rates of hTERC in Han women of CIN were 42.9%, and 52.0% of Uygur women, the two groups without significant difference in statistics(P>0.05). (5) The amplification rates of hTERC in Han women of SCC were 87.5%, and 95.6% of Uygur women, the two groups without significant difference in statistics(P>0.05). (6) The positive rates of hTERC amplification were correlated to the rates of HPV infection in the cytologic specimens of CIN and SCC (r= 0.814, P=0.001). Conclusions: (1) The amplication of hTERC in the squmous cervical cancer and CIN suggests that 3q copy numbers are associated with the severity of cytologic and histologic findings. Therefore, application of the probe set may provide an objective genetic test for the assessment of cells in Pap smears and serves as ascreening test marker for HSIL or CINⅡ/Ⅲwhich may help to determine the progressive potential of individual lesions. (2) There is no difference of the hTERC amplification in Han women patients and Uygur women patients. (3) There are close relations betweem hTERC amplification and HPV infection in CIN and SCC.
Objective: To investigate the clinical significance and amplification of the human telomerase compenent (hTERC) gene in the cytologic specimens of cervix. Methods: The fluorescence signal of 120 cases cytologic samples of cervix were detected by using Interphase FISH in chromosome enumeration double-color DNA probes TERC. 60 cases of cervical intraepithelial neoplasia and 40 cases of squamous cell carcinomas were determined for HPVDNA by the channelization hybridization genechip. Results: (1) in cytological examination: the amplication rates of hTERC in the normal sample were 0%, while 11.1% of the atypical squamous cell of unde-termined significance, 33.3% of the low-grade squamous intraepithelial, 77.8% of the high-grade squamous intraepithelial and 100% of the squamous cell carcinoma showed that extra copies of 3q.TERC copy numbers in HSIL and SCC were significantly higher than that in normal cell, ASCUS and LSIL, and the overall amplification rates of hTERC among groups have statistically significant(P<0.05). (2) in histology biopsy: the amplication rates of hTERC in the cervical intraepithelial neoplasiaⅠlesions were 30%, while 67.5% of the cervical intraepithelial neoplasiaⅡ/Ⅲlesions and 92.5% of the squamous cervical cancer showed that extra copies of 3q. TERC copy numbers in CINⅡ/Ⅲwere significantly higher than that in CINⅠ. The percentage of multiple 3q signals increased with the severity of the cytologic interpretation, the differences were statistically significant (P<0.05). (3) we observed the types of 3q. TERC copy numbers in the cytologic specimens of cervix of normal sample were 2:2, the types of 3q. TERC copy numbers were 2:3、2:4、2:5、3:3、2:6、4:4 in the CIN and SCC. (4) The amplification rates of hTERC in Han women of CIN were 42.9%, and 52.0% of Uygur women, the two groups without significant difference in statistics(P>0.05). (5) The amplification rates of hTERC in Han women of SCC were 87.5%, and 95.6% of Uygur women, the two groups without significant difference in statistics(P>0.05). (6) The positive rates of hTERC amplification were correlated to the rates of HPV infection in the cytologic specimens of CIN and SCC (r= 0.814, P=0.001). Conclusions: (1) The amplication of hTERC in the squmous cervical cancer and CIN suggests that 3q copy numbers are associated with the severity of cytologic and histologic findings. Therefore, application of the probe set may provide an objective genetic test for the assessment of cells in Pap smears and serves as ascreening test marker for HSIL or CINⅡ/Ⅲwhich may help to determine the progressive potential of individual lesions. (2) There is no difference of the hTERC amplification in Han women patients and Uygur women patients. (3) There are close relations betweem hTERC amplification and HPV infection in CIN and SCC.
引文
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