p16、Ki-67检测在宫颈上皮内瘤变诊断及宫颈癌筛查中的价值

The value of p16 and Ki-67 detection in the diagnosis of cervical intraepithelial neoplasia and cervical cancer screening

目的分析抑制基因蛋白(p16)、增殖细胞核蛋白(Ki-67)免疫组化检测在宫颈上皮内瘤变(CIN)诊断及宫颈癌筛查中的应用价值。方法采用免疫组化SP法检测54例CIN、13例宫颈癌、14例正常宫颈黏膜上皮中p16、Ki-67表达水平。比较CIN、宫颈癌、正常宫颈黏膜上皮p16、Ki-67免疫组化结果,并分析p16、Ki-67及两者联合检测鉴别诊断CIN、宫颈癌、正常宫颈黏膜上皮的敏感性、特异性及准确性。结果正常宫颈黏膜上皮中,p16、Ki-67阳性表达率分别为7.14%、28.57%,显著低于CIN、宫颈癌的阳性表达率,差异有统计学意义(P<0.05)。CIN中,p16、Ki-67阳性表达率随CIN等级增加而上升,其中CINⅠ级p16阳性表达率显著低于CINⅡ级、CINⅢ级及宫颈癌,差异有统计学意义(P<0.05)。p16鉴别诊断CIN、宫颈癌的敏感性与Ki-67比较差异无统计学意义(P>0.05),但p16、Ki-67联合诊断的敏感性高于单独的p16、Ki-67检测,差异有统计学意义(P<0.05)。三种检测方法的特异性数据比较差异无统计学意义(P>0.05)。结论 p16、Ki-67阳性表达率随宫颈病变严重程度加重而增高,两者联合检测可有效区分不同等级CIN及宫颈癌,可作为宫颈癌前病变进展的一个敏感标志物。

Objective To analyze the application value of suppressor gene protein(p16)and proliferating cell nuclear protein(Ki-67) immunohistochemical detection in the diagnosis of cervical intraepithelial neoplasia(CIN) and the screening of cervical cancer. Methods Immunohistochemical SP method was used to detect the expression levels of p16 and Ki-67 in 54 cases with CIN,13 cases with cervical cancer,and 14 cases with normal cervical mucosal epithelium. The p16 and Ki-67 immunohistochemical results in patients with CIN,cervical cancer,and normal cervical mucosal epithelium were compared. The sensitivity,specificity,and accuracy of p16,Ki-67 and the combined detection of the two in the differential diagnosis of CIN,cervical cancer,and normal cervical mucosal epithelium were analyzed. Results In normal cervical mucosal epithelium,the positive expression rates of p16 and Ki-67 were 7.14% and 28.57%,respectively,which were significantly lower than that of CIN and cervical cancer,the difference is statistically significant(P<0.05). In CIN,the positive expression rates of p16 and Ki-67 increased with the increasing of CIN grade. The positive expression rate of p16 in CIN at grade I was significantly lower than that in CIN at gradeⅡ,CIN at grade Ⅲ and cervical cancer,the difference is statistically significant(P<0.05). There is no significant difference in the sensitivity between p16 and Ki-67 in the differential diagnosis of CIN and cervical cancer(P>0.05). The sensitivity of p16+Ki-67 was higher than that of p16 and Ki-67 alone,the difference is statistically significant(P<0.05). There is no significant difference in specificity data between the three detections(P>0.05). Conclusion The positive expression rate of p16 and Ki-67 increases with the severity of cervical lesions. The combined detection of the two can effectively distinguish different grades of CIN and cervical cancer,and can be used as a sensitive marker for the progression of cervical precancerous lesions.