【作者】 李素红；

【导师】 李士瑛； 王全红；

【作者基本信息】 山西医科大学 ， 病理学， 2005， 硕士

【摘要】 目的:探讨宫颈浸润性鳞癌（invasive squamous cell carcinoma ofthe cervix,iscc）中 HPV（human papillomavirus,HPV）16/18、3l/33 感染及 P53、P63、P16^INK4A 、P2I^WAF、MDM2 蛋白的表达和意义。研究它们的相关性及与宫颈鳞癌临床病理特征的关系。分析它们在宫颈鳞癌发生、发展中的作用,为临床早期诊断及基因治疗提供依据。 方法:制作包含 120 例 ISCC 的 240 个点的组织芯片 2 个,采用原位杂交 和免疫组织化学 SP 法检测 106 例 ISCC、10 例上皮内瘤变（cervica] intraepithelial neoplasia,CIN）10 例宫颈正常鳞状上皮（normal cervical epithelium,NCE）中 HPVl6/18、31/33 和 P53、P63、P16INK4A、P21^WAF1、MDM2 的表达。应用 SPSSl2.5 统计软件分析结果。 结果:1、HPV16/18 型在 ISCC 中高表达（53.77%）,与 CIN 组和 NCE 组 比较差异显著（P<O.05）,其阳性率与临床病理参数无明显相关性（P> 0.05）; 2、HPV31/33 阳性表达率在宫颈各组织中的差异无统计学意义（P>0.05）,其表达与淋巴结转移及宫颈浸润深度相关（P<O.05）; 3、P53 蛋白在 ISCC、CIN 和 NCE 中的阳性表达率差异有统计学意义（ P<0.01）,与组织学分级和淋巴结转移呈正相关:III 级表达明显高于I—II 级（P<0.01）,有淋巴结转移者明显高于无淋巴结转移者（P<O.01）。 4、P63 蛋白在 ISCC 中的表达明显高于 CIN 和 NCE 组,差异有显著性（ P<O.05）,P63 蛋白表达与组织学分级呈正相关,III 级表达高于 I—II级（P<0.05）。 5、P16^INK4A 蛋白在 ISCC 组的表达显著高于 NCE 和 CIN 组,差异有统计 学意义（P=O.003）。P16INK4A 表达与组织学分级正相关:III 级宫颈鳞癌 P16INK4A 阳性表达率显著高于 I—II 级（P<O.01）。更多还原

【Abstract】 Objective:To study the expression and significance of HPV 16/18 . 31 / 33 DNA nd P5 3 , p63 , P 16IK4A , P21 wAFl.and MDM2 proteins in invasive squamous ell carcinoma of cervix（ISCC）.To investigate the correlation of HPV 16 / 18 , 31 / 33 DNA and proteins referred to above and the relationship between the iomarkers and clinical pathological parameters.To analyse the significance of he biomarkers in the occurrence and development of ISCC SO as to provide the aluable evidence for the early clinical diagnosis and genetic therapy of ISCC . Method : 120 cases of ISCC were embedded in 240 spots tissue microarrays.In Situ Hybridization（ISH）was used to detect the expression ofHPVl6/ 18 , 31 / 33 DNA and the SP immunohistochemical method was performed to research the expression ofp53、P16INK4A,P21wAF1,P63 and MDM2 protein in ISCC,CIN and NCE.Results was assessed by SPSS vision 12.5. Results:1,The positive expression rate ofHPVl6/18 in ISCC was markedly higher than in CIN and NCE（P<0.05）.No correlation was found between HPV 16/18 and clinical pathological parameters. 2.There iS no abvious difference about HPV3 1/33 expression in ISCC , C1N and NSE（P>O . 05） . but we found the significant difference between HPV3 1/33 and lymph node transferation. 3 . The positive expression rate of P53 protein was 50 % in ISCC , which was significantly higher than in the CIN and NSE . The positive rates of P5 3 protein expression were significantly higher in the cases of histological grade III than the cases of histological grade I-II and the cases with lymph node metastasis than those without lymph node metastasis（P<0.01） 4.We found the difference of the expresslon of P63 between ISCC and CIN,ISCC and NCE（P<0.05）.The positive rates of P63 were significantly higherin the cases of pathological grade III than those in grade I—II. 5 . The positive expression rate of P 16^INK4A had the significant difference between ISCC and CIN,ISCC and NCE.Significant relationship was observed between P 16INK4A protein expression and differentiated grades of the ISCC. 6 . The difference of P2 1 wAF1 protein was significant among ISCC . C1N . and NCE（P<0 . 01） . The positive expression rate of P21WAF1 protein in the cases of deeper invasion was significantly higher than those in the cases of superficial invasion（P<O.05）. 7 , The positive expression rate of MDM2 was 50 . 94 % in ISCC.Difference was significant between ISCC and CIN,ISCC and NCE.No significant correlation was observed between MDM2 protein expression and every clinical pathological parameter of ISCC. 8 , We found the positive correlation between P53 , P63 , P16INK4A ,P21wAF1, MDM2 protein and HPV 16/18 DNA.but no correlation and HPV 31/33 DNA. 9.We found that P53 protein expression is positively correlated with MDM2 protein . XL test showed that expression of P63 protein have a positive coI.relation with P 16^INK4A and P21^WAF1 protein,but a negative correlation with MDM2 protein. Conclusion:1.There was a higher positive expression ofHPVl6/18 than that of HPV3 1/33 in ISCC and we found that mtp53 protein expression rate was very high because HPV DAN was positive in ISCC.The results of our study indicate that the positive expression rate of P 16INK4A,P21 wAF1 was high , but not low in ISCC . The overexpression of MDM2 proteinsuggested that MDM2 gene might play a important role as an oncogene on the occurrence in ISCC.But the positive expression of P 16^INK4A.P21^wAF1hint that P 16INK4A and P21 wAF1 genes might not act as a suppressor—gene only on the occurrence and development in ISCC.The overexpression of P63 protein in ISCC suggested that p63 gene might be oncogene but not suppressor — gene on the occurence and development in ISCC更多还原