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目的探讨脆性组氨酸三联体(fragile histidine triad,FHIT)、P16INK4a与视黄酸受体β(retinoic acid receptor-beta,RARβ)蛋白在新疆维吾尔族妇女宫颈上皮内瘤变(cervical intra-epithelial neoplasia,CIN)及宫颈癌中的表达及其意义。方法采用免疫组化链霉素抗生物素蛋白-过氧化物酶链接(SP)法检测20例慢性宫颈INK4a炎、30例CIN(CINⅠ、CINⅡ、CINⅢ各10例)以及40例浸润性宫颈鳞癌组织标本中FHIT、P16INK4a及RARβ蛋白的表达。结果(1)FHIT蛋白阳性表达率依次为慢性宫颈炎(90.00%)>CIN(66.67%)>浸润性宫颈鳞癌INK4a(27.50%)(P=0.000);P16和RARβ蛋白阳性表达率依次为浸润性宫颈鳞癌(82.50%;90.00%)>CIN(46.67%;53.33%)>慢性宫颈炎(0.00%;10.00%)(P=0.000;P=0.000)。(2)在宫颈各组织中,FHIT蛋白INK4a与P16INK4a蛋白表达呈负相关(r=-0.384,P=0.000);FHIT蛋白与RARβ蛋白表达呈负相关(r=-0.291,P=0.006);P16INK4a蛋白与RARβ蛋白表达呈正相关(r=0.445,P=0.000)。结论抑癌基因FHIT表达缺失与P16INK4a和RARβ过度表达与宫颈癌的发生发展密切相关,并且FHIT、P16INK4a、RARβ具有协同作用。FHIT蛋白与P16INK4a蛋白和RARβ蛋白的联合检测可作为宫颈癌早期诊断和宫颈癌进展的分子指标。
Objective To investigate the expression of FHIT, P16INK4a and retinoic acid receptor-beta (RARβ) in cervical intra-epithelial neoplasia , CIN) and cervical cancer and its significance. Methods Twenty cases of chronic cervicitis INK4a, 30 CIN (CINⅠ, CINⅡ, CINⅢ, 10 cases) and 20 cases of invasive cervical squamous cell carcinoma were detected by immunohistochemical streptavidin-peroxidase linked enzyme linked immunosorbent assay Expression of FHIT, P16INK4a and RARβ in cancer tissue samples. Results (1) The positive rates of FHIT protein were CIN (66.67%)> INK4a (27.50%) (P = 0.000). The positive rates of P16 and RARβ were Invasive cervical squamous cell carcinoma (82.50%; 90.00%)> CIN (46.67%; 53.33%)> chronic cervicitis (0.00%; 10.00%) (P = 0.000; P = 0.000). (2) There was a negative correlation between the expression of INK4a and P16INK4a protein in cervical tissues (r = -0.384, P = 0.000); FHIT protein was negatively correlated with RARβ protein expression (r = -0.291, P = 0.006) P16INK4a protein and RARβ protein expression was positively correlated (r = 0.445, P = 0.000). Conclusion The loss of FHIT gene expression and the overexpression of P16INK4a and RARβ are closely related to the occurrence and development of cervical cancer. FHIT, P16INK4a and RARβ have synergistic effects. The combined detection of FHIT protein, P16INK4a protein and RARβ protein may serve as a molecular marker for early diagnosis of cervical cancer and progression of cervical cancer.