联合检测脱落细胞中p16^(INK4A)、Brn3a和端粒酶等因子的表达对预测宫颈病变进展的价值

The value of combined detection of p16^(INK4A), Brn3a, telomerase and other biomarkers in cervical cytology for predicting the progression of cervical neoplasia

目的 :检测p16INK4A、Brn3a、端粒酶及人宫颈癌基因(human cervical cancer oncogene,HCCR)在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)中的表达,探讨其对于预测宫颈病变进展的意义。方法 :262例宫颈脱落细胞标本取自宫颈液基细胞学检查(liquid-based cytology test,LCT)残液制成的石蜡标本,包括30例正常宫颈细胞、80例意义不明不典型鳞状细胞(atypical squamous cells of undetermined signiicance,ASCUS)、72例低级别鳞状上皮病变(low-grade squamous intraepithelial lesion,LSIL)、50例高级别鳞状上皮病变(high-grade squamous intraepithelial lesion,HSIL)和30例浸润性宫颈鳞癌。采用免疫细胞化学法检测脱落细胞石蜡切片中p16INK4A、Brn3a、端粒酶及HCCR的表达水平。结果 :与正常宫颈细胞相比,ASCUS和LSIL标本中p16INK4A和Brn3a表达水平均升高(P<0.05);与ASCUS和LSIL相比,HSIL和浸润性宫颈鳞癌中p16INK4A、Brn3a、端粒酶及HCCR表达水平显著升高(P<0.05)。与最终病理诊断结果为慢性炎性反应和宫颈湿疣的患者相比,ASCUS中诊断为CIN1级的患者p16INK4A表达水平升高(P<0.05);诊断为CIN2+级的患者p16INK4A和Brn3a表达水平均升高(P<0.05)。LSIL中病理诊断结果为CIN2+级的患者与慢性炎性反应和宫颈湿疣病例相比,p16INK4A和Brn3a表达水平均明显升高(P<0.05)。ASCUS和LSIL患者中p16INK4A和Brn3a表达水平之间具有显著相关性(r=0.580,P<0.001)。结论 :检测p16INK4A、Brn3a、端粒酶及HCCR水平有助于鉴别诊断ASCUS/LSIL和HSIL/浸润性宫颈癌,而联合检测p16INK4A和Brn3a有助于预测ASCUS和LSIL的病变进展。

Objective： To study the expressions of p16^INK4A, Brn3a, telomerase and human cervical cancer oncogene （HCCR） in cervical intraepithelial neoplasia （CIN）, and to estimate their values for predicting the progression of cervical lesions. Methods： Paraffin specimens of 262 cases were all from the residue of patients＇ liquid-based cytology test （LCT） samples, including 30 normal cases, 80 cases of atypical squamous cells of undetermined significance （ASCUS）, 72 cases of low-grade squamous intraepithelial lesions （LSIL）, 50 cases of high-grade squamous epithelial lesions （HSIL） and 30 cases of invasive squamous cell carcinoma. The expression levels of p16^INK4A, Brn3a, telomerase and HCCR in these samples were detected using immunocytochemistry. Results： The expression levels of p16^INK4A and Brn3a in ASCUS and LSIL specimens were significantly higher than those in normal cells （P 〈 0.05）. Compared to ASCUS and LSIL, the expression levels of p16^INK4A, Brn3a, telomerase and HCCR in HSIL and invasive squamous cell carcinoma were significantly higher （P 〈 0.05）. Among ASCUS, both the expression of p16^INK4A in cases that had pathological diagnosis of CIN1 and the expressions of p16^INK4A and Brn3a in cases that had pathological diagnosis of CIN2＋ were significantly higher than those had pathologicaldiagnosis of chronic cervicitis or cervical condyloma （P 〈 0.05）. Among LSIL, the expressions of p16^INK4A and Brn3a in cases that had pathological diagnosis of CIN2＋ were significantly higher than those had pathological diagnosis of chronic cervicitis or cervical condyloma （P 〈 0.05）. Moreover, the expressions of p16^INK4A and Brn3a in ASCUS and LSIL had a strong relationship （r = 0.580, P 〈 0.001）. Conclusion： The expression levels of p16~NK4A, Brn3a, telomerase and HCCR can help distinguish HSIL and invasive squamous cell carcinoma from ASCUS and LSIL, and combined detection of p16^INK4A and Brn3a maybe assist in predicting the progression of ASCUS and LSIL.