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目的:探讨宫颈病变中内质网分子伴侣与HLA-Ⅰ和HPV16表达的关系。方法:通过免疫组化SP法检测内质网分子伴侣和HLA-Ⅰ类分子在慢性宫颈炎、宫颈上皮内瘤变(CIN)和宫颈癌患者石蜡包埋组织中的表达水平;以PCR技术检测相应标本中HPV16感染的情况。结果:CIN中分子伴侣钙连接蛋白(CNX)、钙网蛋白(CRT)、TAP相关蛋白(Tapasin)、蛋白质二硫异构体Erp57和HLA-Ⅰ抗原的表达下调和缺失率分别为15.6%/21.9%、21.9%/15.6%、28.1%/15.6%、20.3%/21.9%和31.2%/29.7%。在宫颈癌组织中表达下调和缺失率分别为22.2%/30.0%、20.6%/34.9%、23.8%/28.6%、30.0%/28.6%和31.7%/47.6%,并且随着宫颈病变的加重,其表达下调和缺失率增加(P<0.05)。CRT和ERp57与宫颈癌分化程度密切相关,Tapasin、CNX、ERp57与淋巴结转移密切相关,Tapasin与FIGO临床分期密切相关,表达差异均有统计学意义(P<0.05)。在CIN中HLA-Ⅰ与CNX、CRT、ERp57表达下调呈正相关,HPV16感染与CRT、ERp57表达呈负相关。宫颈癌中HLA-Ⅰ与CRT、ERp57和Tapasin表达下调呈正相关,HPV16感染与Tapasin、CNX、CRT、ERp57表达呈负相关。结论:在CIN和宫颈癌组织中内质网分子伴侣表达下调,可能是影响HLA-Ⅰ类分子在细胞表面正常表达的重要原因之一。而HPV16也可能利用此途径逃避免疫监视,促进宫颈癌的发生和发展。
Objective: To investigate the relationship between the endoplasmic reticulum molecular chaperones and the expression of HLA-Ⅰ and HPV16 in cervical lesions. Methods: The expressions of endoplasmic reticulum chaperones and HLA-Ⅰ molecules in chronic cervicitis, cervical intraepithelial neoplasia (CIN) and cervical cancer tissues were detected by immunohistochemical SP method. HPV16 infection in the corresponding specimens. Results: The down-regulation and deletion rates of CNX, CRT, Tapasin, Erp57 and HLA-Ⅰ antigen in CIN were 15.6% 21.9%, 21.9% / 15.6%, 28.1% / 15.6%, 20.3% / 21.9% and 31.2% / 29.7% respectively. The rates of down-regulation and loss in cervical cancer tissues were 22.2% / 30.0%, 20.6% / 34.9%, 23.8% / 28.6%, 30.0% / 28.6% and 31.7% / 47.6%, respectively. With the increase of cervical lesions, The expression was down-regulated and the deletion rate was increased (P <0.05). CRT and ERp57 were closely related to the degree of cervical cancer differentiation. Tapasin, CNX and ERp57 were closely related to lymph node metastasis. Tapasin was closely related to the clinical stage of FIGO, and the difference was statistically significant (P <0.05). There was a positive correlation between HLA-Ⅰ and CNX, CRT and ERp57 expression in CIN, and a negative correlation between HPV16 infection and CRT and ERp57 expression. The negative correlation between HLA-Ⅰ and CRT, ERp57 and Tapasin expression in cervical cancer was negatively correlated with the expression of Tapasin, CNX, CRT and ERp57. CONCLUSION: Down-regulation of endoplasmic reticulum molecular chaperones in CIN and cervical cancer may be one of the important factors affecting the normal expression of HLA class I molecules on the cell surface. The HPV16 may also use this route to evade immune surveillance and promote the occurrence and development of cervical cancer.