增殖细胞核抗原及肿瘤转移抑制基因nm23在外阴鳞状细胞癌的表达及其临床意义

Studies on the expression of PCNA and nm23 protein in squamous cell carcinoma of the vulva and its clinical significance

目的通过检测增殖细胞核抗原(PCNA)及nm23在不同外阴组织中的表达情况,了解PCNA指数及nm23蛋白表达与外阴鳞状细胞癌临床参数的关系及其临床意义。方法采用ABC免疫组织化学方法,对正常外阴上皮、VIN及外阴鳞状细胞癌组织中PCNA及nm23的表达进行检测。结果 nm23蛋白均在正常外阴上皮、VIN及外阴鳞状细胞癌中表达;外阴鳞状细胞癌较VIN及正常外阴上皮显著降低(P<0.05),不同级别VINnm23蛋白阳性值差异无统计学意义(P>0.05);VINⅡ、Ⅲnm23蛋白表达差异有统计学意义(P<0.05)。高分化癌与中分化癌及高分化癌与低分化癌之间nm23蛋白表达的阳性值差异有统计学意义(P<0.05),中分化癌与低分化癌nm23蛋白的表达差异无统计学意义(P>0.05);淋巴结有转移者,原发灶nm23阳性值与转移灶nm23蛋白阳性值差异无统计学意义(P>0.05);但淋巴结无转移者原发灶与淋巴结有转移者原发灶nm23蛋白阳性值差异有统计学意义(P<0.05),nm23蛋白的表达与临床分期及预后有关,而与绝经状态及年龄无关。对PCNA在不同外阴组织表达进行检测表明正常外阴上皮、VIN及外阴鳞状细胞癌PCNA指数差异有统计学意义(P<0.05),PCNA指数随VIN级别的增加而升高,VINⅠ与ⅢPCNA指数差异有统计学意义(P<0.05),而VINⅠ与Ⅱ及VINⅡ与ⅢPCNA指数差异无统计学意义(P>0.05);外阴鳞状细胞癌PCNA指数随着组织学分级的增加而升高,其中Ⅰ、Ⅱ级PCNA指数差异无统计学意义(P>0.05);而Ⅲ级与Ⅰ、Ⅱ级PCNA指数差异有统计学意义(P<0.05)。淋巴结有转移者原发灶PCNA指数较淋巴结无转移者原发灶PCNA指数明显升高,但两者差异无统计学意义(P>0.05);在淋巴结有转移患者PCNA指数在原发灶与转移灶之间差异有统计学意义(P<0.05),转移灶较原发灶高。PCNA指数随着外阴鳞状细胞癌临床期别增加而升高(P<0.05),Ⅰ期与Ⅳ期PCNA指数差异有统计学意义(P<0.05),年龄及绝经状态对PCNA指数无影响,死亡患者nm23蛋白阳性值低,PCNA指数高,差异有统计学意义(P<0.05)。结论 VIN和外阴鳞状细胞癌PCNA指数较正常外阴上皮高而nm23蛋白表达降低,在外阴鳞状细胞癌中,随着组织学分级增加,PCNA有升高趋势,nm23蛋白表达有下降趋势,反之亦然。Nm23蛋白的表达与肿瘤转移呈负相关,PCNA指数与肿瘤转移呈正相关,故对于PCNA指数高,而nm23蛋白表达阴性的未转移病例应加强随访,密切注意病情变化。

Objective To explore the expression of proliferating cell nuclear antigen（PCNA） and nm23 protein in paraffin-embeded biopsies from vulval tissue and Its clinical significance.Methods Through immunohistochemistry（ABC）,PCNA-LI and the expression of nm23 was detected in normal vulvar epithelial cells,vulvar intraepithelial neoplasia（VIN）,and squamous cell carcinoma of the vulva.Results The expression of nm23 protein in squamous cell carcinoma of the vulva was significantly lower than that in VIN and normal vulvar epithelial cells（P0.05）.The positive value for nm23 protein of different grades showed no statistically significant difference（P0.05）.The expression of nm23 showed statistically significant difference between VIN Ⅱ and Ⅲ nm23（P0.05）,and also between well-differentiated carcinoma and moderately differentiated carcinoma（P0.05）,but not between moderately differentiated carcinoma and poorly differentiated carcinoma.We demonstrate that the positive value of nm23 protein in patients with lymph node metastases was lower than that in patients without lymph node metastases,with no statistically significant difference.The expression of nm23 protein was found to be associated with clinical stage and prognosis but not menopausal status and age.PCNA-LI showed statistically significant difference in normal vulvar epithelial cells,VIN,and squamous cell carcinoma of the vulva（P0.05）,which increased with the increase of VIN grade.PCNA-LI in squamous cell carcinoma of the vulva increased with the histological grade,with no statistically significant difference between the gradeⅠand gradeⅡ.These indicators in patients with lymph node metastases was increased than that in patients without lymph node metastases,but with no statistically significant difference（P0.05）,which were found to be significantly higher in secondary site of tumor than primary site of tumor.PCNA-LI in invasive vulval carcinoma was increasing with advancing histological grade and clinical stages.However,the PCNA-LI was found to be not related to the menopausal status and age（P0.05）.Conclusion In VIN and squamous cell carcinoma of the vulva,PCNA-LI is higher than that in normal vulvar epithelial cells,while the expression of nm23 is lower.PCNA-LI was increased from normal epithelium to invasive squamous carcinoma.The positive value of nm23 protein was gradually decreased.And nm23 protein may inhibit metastasis of tumor.