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目的探讨宫颈鳞状细胞癌(SCC)及宫颈上皮内肿瘤(CIN)组织中人乳头瘤病毒(HPV)16感染与端粒酶反转录蛋白(hTERT)、抑癌基因p21waf1和增生抗原Ki67表达的关系及其意义。方法在130例宫颈组织中利用组织芯片技术结合原位杂交技术检测HPV16感染及结合免疫组织化学技术检测hTERT、Ki67、p21waf1的表达。结果(1)HPV16杂交信号阳性率及hTERT、Ki67表达在CINⅡ～Ⅲ级、原位癌、浸润性鳞癌组织中都显著高于正常宫颈组织(P均<0.05),浸润癌也显著高于CIN(P均<0.05),CIN三级之间差异也具统计学意义(P均<0.05)。(2)p21waf1仅在浸润性鳞癌组织中的阳性率显著低于正常宫颈组织(P<0.05),其他组别之间差异无统计学意义(P均>0.05)。(3)HPV16感染及Ki67表达与hTERT表达均呈正相关(P<0.05,r=0.339;P<0.05,r=0.398);HPV16感染、hTERT及Ki67表达与p21waf1表达均呈负相关(P<0.05,r=0.337;P<0.05,r=0.248;P<0.05,r=0.446);HPV16感染与Ki67表达无相关性(P>0.05)。结论宫颈上皮内肿瘤及宫颈鳞状细胞癌组织中hTERT、p21waf1、Ki67表达的改变可能与HPV16感染有关,且互相作用,共同影响CIN的发展及宫颈鳞癌的发生。这些指标综合分析可能为阐明HPV16的恶性转化机制以及为提高宫颈鳞癌及其癌前病变诊断率提供参考依据。组织芯片技术是高效的研究基因及其表达产物的技术平台。
Objective To investigate the relationship between human papillomavirus (HPV) 16 infection and the expression of telomerase reverse transcriptase (hTERT), tumor suppressor gene p21waf1 and proliferating antigen Ki67 in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN) Relationship and its significance. Methods Tissue microarray technique combined with in situ hybridization was used to detect the expression of hTERT, Ki67 and p21waf1 in 130 cases of cervical tissues by HPV 16 infection and immunohistochemistry. Results (1) The positive rate of HPV16 hybridization and the expression of hTERT and Ki67 in CINⅡ ~ Ⅲ grade, in situ carcinoma and invasive squamous cell carcinoma were significantly higher than those in normal cervical tissue (all P <0.05), and invasive carcinoma was also significantly higher than CIN (P <0.05). There was also significant difference between the three levels of CIN (all P <0.05). (2) The positive rate of p21waf1 in invasive squamous cell carcinoma was significantly lower than that in normal cervical tissue (P <0.05). There was no significant difference among other groups (all P> 0.05). (3) HPV16 infection and Ki67 expression were positively correlated with hTERT expression (P <0.05, r = 0.339; P <0.05, r = 0.398); HPV16 infection, hTERT and Ki67 expression were negatively correlated with p21waf1 expression , r = 0.337; P <0.05, r = 0.248; P <0.05, r = 0.446). There was no correlation between HPV16 infection and Ki67 expression (P> 0.05). Conclusion The changes of hTERT, p21waf1 and Ki67 expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma may be related to HPV16 infection and interact with each other to affect the development of CIN and the occurrence of cervical squamous cell carcinoma. The comprehensive analysis of these indicators may provide a reference for elucidating the mechanism of malignant transformation of HPV16 and improving the diagnostic rate of cervical squamous cell carcinoma and its precancerous lesions. Tissue chip technology is an efficient platform for studying genes and their expression products.