B7-H4及Fas、FasL与宫颈癌免疫逃逸机制的关系

目的:检测免疫共刺激分子B7-H4及Fas、FasL在不同宫颈组织中的表达，研究三者的异常表达与宫颈癌免疫逃逸机制的关系。方法:选择陕西省肿瘤医院病理科2014-2018年的石蜡包埋标本162例，采用免疫组织化学方法检测20例正常宫颈、30例宫颈上皮内瘤变(CIN)和112例I期-IV期宫颈癌组织中B7-H4及Fas、FasL的表达水平。结果:B7-H4在正常宫颈组、CIN组、宫颈癌组的阳性表达率分别为0、20.0%、47.32%，两两相比，具有显著性差异（P<0.05）。在112例宫颈癌病例中FIGO临床分期I期至IV期各期别宫颈癌组织B7-H4的阳表达率分别为16.67%、43.18%、70.83%、85.71%，各组间相比差异具有统计学意义。正常对照组Fas的阳性表达率是85.00％，CIN组43.33％，宫颈癌组41.96％，正常组与CIN、正常组与宫颈癌组相比差异均具有统计学意义（P<0.05），CIN组与宫颈癌组相比，无明显差异（P>0.05）。FasL的阳性表达率在正常组为20.00%，CIN组为50.00%，宫颈癌组为56.25%，正常组与CIN、宫颈癌组比较，差异具有统计学意义(P<0.05)，CIN组与宫颈癌组比较无显著差异;B7-H4阳性宫颈癌组Fas阳性表达率28.30%明显较B7-H4阴性宫颈癌组Fas阳性表达率54.24%低，差异具有统计学意义（P<0.05）；而B7-H4阳性宫颈癌组FasL阳性表达率79.25%明显高于B7-H4阴性宫颈癌组FasL阳性表达率35.59%，差异具有统计学意义（P<0.05）。结论:负性免疫共刺激分子B7-H4和Fas、FasL凋亡蛋白在宫颈癌的发生、进展中起到了重要作用，其协同作用可能为宫颈癌细胞逃逸机体免疫的机制之一。

Relationship between B7-H4，Fas，FasL and immune escape mechanism of cervical cancer

Objective:To detect the expression of B7-H4，Fas and FasL in different cervical tissues，and to study the relationship between the abnormal expression of B7-H4，Fas,FasL and the immune escape mechanism of cervical cancer.Methods:The expression of B7-H4，Fas and FasL in 20 cases of normal cervix，30 cases of cervical intraepithelial neoplasia (CIN) and 112 cases of stage I-IV cervical cancer were detected by immunohistochemistry.Results:The positive rate of B7-H4 on normal cervix，CIN and cervical cancer tissue was 0，20.0%，47.32% respectively，compared with the differences between groups with statistical significance (P<0.05).In 112 cases of cervical cancer，the positive expression rate of B7-H4 in different stages of FIGO clinical stage I to IV was 16.67% in stage I，43.18% in stage II，70.83% in stage III and 85.71% in stage IV，respectively.There was significant difference between each group (P<0.05).The positive expression rate of Fas was 85.00% in the normal control group，43.33% in the CIN group and 41.96% in the cervical cancer group.The difference between the normal group and CIN，the cervical cancer group was statistically significant (P<0.05)，no significant difference between CIN and cervical cancer group (P>0.05).The positive expression rate of FasL in normal cervix，CIN and cervical cancer tissues were 20.00%，50.00%，56.25% respectively.Difference between the CIN，cervical cancer group and normal group had statistical significance (P<0.05).Compared CIN and cervical cancer group，the difference had no sense of statistics.Fas positive expression rate (28.30%) on B7-H4 positive cervical cancer was lower than that in B7-H4 negative cervical cancer group (54.24%)，statistically significant difference (P<0.05)，while FasL positive expression rate on B7-H4 positive cervical cancer (79.25%) was significantly higher than B7-H4 negative cervical cancer group one (35.59%)，statistically significant difference(P<0.05).Conclusion:Negative immune stimulating molecules B7-H4 and apoptosis proteins Fas，FasL play important roles in the occurrence and progress of cervical cancer.The synergy may be one of the mechanisms for cervical cancer cells escape the body's immune system.Independently or jointly test of B7-H4 and Fas，FasL can help us to predict cervical cancer biology behavior，as one of the reference indexes for cervical cancer prognosis evaluation.Intervention on expressions of B7-H4 and Fas，FasL apoptosis will probably become a new immunotherapy target for cervical cancer.