P16^(INK4A)免疫组化染色在CIN2患者分流中的作用

Value of P16^(INK4) Aimmunohistochemistry staining in triage of cervical intraepithelial neoplasia grade 2

目的评价P16INK4A在降低子宫颈上皮内瘤变(CIN)2诊断级别及预测锥切术后CIN2+的作用。方法回顾性分析2010年1月至2012年12月及2014年9月至2015年4月在北京大学第一医院妇产科门诊阴道镜指引下多点活检病理诊断CIN2的444例病例资料,将2014年9月至2015年4月107例CIN2患者设为A组,对HE染色形态学诊断CIN2的组织蜡块再次连续切片,行P16INK4A免疫组织化学染色,全部采用P16INK4A分流;将2010年1月至2012年12月337例CIN2患者设为B组,CIN的诊断根据HE染色的形态学结果得出。分析P16INK4A免疫组化染色在降低患者诊断级别及提高预测锥切术后CIN2+的作用。结果在107例行P16INK4A免疫组化染色的CIN2患者中,P16INK4A阳性者85例,占79.4%(85/107);P16INK4A灶阳者16例,占15.0%(16/107);P16INK4A阴性者6例,占5.6%(6/107)。444例阴道镜下活检病理诊断的CIN2预测锥切术后病理诊断为CIN2+的阳性预测值为62.4%(277/444),在采用P16INK4A免疫组化染色分流的A组中可降低20.6%(22/107)患者的病理诊断级别,同时可将子宫颈活检病理诊断的高级别子宫颈鳞状上皮内病变(HSIL)锥切术后诊断CIN2+的阳性预测值增加至77.6%。B组与A组中P16INK4A阳性组相比较,锥切术前后病理一致性的差异有统计学意义(χ2=8.626,P=0.003);B组与P16INK4A灶阳组相比较,锥切术前后病理一致性的差异无明显统计学意义(χ2=7.818,P=0.098);B组与P16INK4A阴性组相比较,锥切术前后病理一致性的差异有统计学意义(χ2=18.143,P=0.001)。结论子宫颈活检组织病理诊断的CIN2采用P16INK4A免疫组化染色分流可降低20.6%患者的诊断级别,提高预测锥切术后CIN2+的能力,以减少不必要的干预。

Objective To evaluate the value of P16^INK4A in downgrading the diagnosis of cervical intraepithelial neoplasia 2(CIN2)and in predicting higher grade of lesions after loop electrosurgical excision procedure (LEEP).Methods Totally 444 CIN2 cases were retrospectively analyzed,which were diagnosed by colposcope-directed cervical multi-point biopsy in the Outpatient Department of Obstetrics and Gynecology in Peking University First Hospital from September 2014 to April 2015(group A,107 cases)and January 2010 to December 2012(group B,337 cases).In group A,P16^INK4A immunohistochemistry staining was performed for triage on the basis of morphological diagnosis of HE staining.Diagnosis of CIN2 of group B was based on morphological results of HE staining.Results In group A,85 cases,16cases and 6 cases were positive,focus-positive and negative for P16^INK4A,accounting for 79.4%(85/107),15.0%(16/107)and 5.6%(6/107),respectively.The positive predictive value (PPV)of CIN2+diagnosed by biopsy under vaginoscopy in 444 patients was 62.4%(277/444).In group A,the diagnostic grade of patients could be reduced by 20.6%(22/107)when P16^INK4A immunohistichemical staining was performed for triage,and the PPV of CIN2+in the diagnosis of cervical squamous epithelial lesion (HSIL)after cone resection could be increased to 77.6%.Compared with group B, preoperative and postoperative pathological consistency of P16^INK4A positive group in group A had statistical significance (x^2=8.626,P=0.003),and the focus-positive group had no statistical significance (x^2=7.818,P=0.098),and the negative group had statistical significance (x^2=18.143,P=0.001).Conclusion P16^INK4A immunohistichemical staining can downgrade 20.6% pathological diagnosis of CIN2 in patients with cervical biopsy and improve the prediction ability of postoperative CIN2+to reduce unnecessary intervention.