子宫内膜癌及子宫内膜不典型增生患者免疫组化特征与保留生育疗效的相关因素分析

Analysis of immunohistochemical characteristics and fertility preservation in patients with endometrial carcinoma and endometrial atypical hyperplasia

目的:探讨年轻子宫内膜癌(EC)及子宫内膜不典型增生(AH)患者免疫组化特征与保留生育治疗疗效的关系。方法:回顾分析2010年1月至2020年8月北京大学人民医院收治的EC(40例)及AH(47例)患者的临床资料及免疫组化结果,采用醋酸甲羟孕酮(MPA)或醋酸甲地孕酮(MA)口服,联用促性腺激素释放激素激动剂(GnRH-a)和(或)左炔诺酮宫内缓释系统(LNG-IUS),根据开始治疗后9个月内是否完全缓解(CR)将患者分为组1≤9个月达CR组;组29个月未达CR组(包括PR、NC、PD及复发患者),进行统计学分析。结果:组1使用MPA、MPA+GnRH-a、MPA+LNG-IUS、MPA+GnRH-a+LNG-IUS例数分别为27例、4例、2例、1例,组2使用MA、MPA、MPA+GnRH-a、MPA+LNG-IUS、MPA+GnRH-a+LNG-IUS分别为2例、22例、4例、3例、4例,差异无统计学意义(P>0.05)。组1中p16、p53、PTEN阳性表达率分别为81.0%(17/21)、32.0%(8/25)、27.3%(6/22),ER、PR、Ki-67在癌灶中表达率的中位数分别为70%(60%,80%)、80%(50%,90%)、10%(8.75%,20%);组2中p16、p53、PTEN阳性表达率分别为91.7%(22/24)、51.5%(17/33)、28.0%(7/25),ER、PR、Ki-67在癌灶中表达率的中位数分别为70%(50%,80%)、80%(65%,90%)、30%(17.5%,30%)。两组的ER、PR、p16、p53、PTEN表达率比较,差异无统计学意义(P>0.05),而组2的Ki-67表达率明显高于组1,差异有统计学意义(P<0.05)。Ki-67与p53联合诊断试验如Ki-67<20%且p53定性为阴性,则缓解率为70.6%(12/17),若p53阳性则缓解率为50%(3/6),如Ki-67≥20%,p53定性为阴性或阳性,其缓解率分别仅为26.7%(4/15)和26.3%(5/19)。结论:保留生育治疗前对刮宫标本进行免疫组化染色有助于了解EC与AH患者的预后,Ki-67表达率对保留生育治疗疗效的预测意义较大。Ki-67<20%且p53阴性更倾向于疾病缓解,而如果Ki-67≥20%,则不能如期缓解可能性大。

Objective:To investigate the relationship between immunohistochemical characteristics and the efficacy of fertility preservation treatment in patients with endometrial cancer(EC)and endometrial atypical hyperplasia(AH).Methods:The clinical data and immunohistochemical results of 40 patients with EC and 47 patients with AH admitted to Peking University People's Hospital from January 2010 to August 2020 were retrospectively analyzed.Medroxyprogesterone acetate(MPA)or Megestrol acetate(MA)were orally administered,Combined with gonadotropin releasing hormone agonist(GnRH-a)and/or levonorgestrel intrauterine sustained release system(LNG-IUS).Patients were divided into two groups according to whether complete remission(CR)was achieved within 9 months after starting treatment:Group 1:CR reached within 9 months;Group 2:CR not reached within 9 months(including PR,NC,PD and relapsed patients),for statistical analysis.Results:The number of cases using MPA,MPA+GnRH-a,MPA+LNG-IUS,MPA+GnRH-a+LNG-IUS in Group 1 was 27,4,2,and 1 respectively,and the number of cases using MA,MPA,MPA+GnRH-a,MPA+LNG-IUS,MPA+GnRH-a+LNG-IUS in Group 2 was 2,22,4,3,and 4 respectively,with no significant difference(P>0.05).In Group 1,the positive expression rates of p16,p53 and PTEN were 81.0%(17/21),32.0%(8/25)and 27.3%(6/22),respectively,and the median expression rates of ER,PR and Ki-67 were 70%(60%,80%),80%(50%,90%)and 10%(8.75%,20%),respectively.The positive expression rates of p16,p53 and PTEN in Group 2 were 91.7%(22/24),51.5%(17/33)and 28.0%(7/25),respectively,and the median expression rates of ER,PR and Ki-67 were 70%(50%,80%),80%(65%,90%)and 30%(17.5%,30%),respectively.The expression rates of ER,PR,p16,p53 and PTEN were not significantly different between the two groups(P>0.05),while the expression rate of Ki-67 in Group 2 was significantly higher than that in Group 1,and the difference was statistically significant(P<0.05).Combined diagnostic test of Ki-67 and p53:if Ki-67 was less than 20%and p53 was negative,the remission rate was 70.6%(12/17),if p53 was positive,the remission rate was 50%(3/6);if Ki-67 was more than 20%,and p53 was negative or positive,the remission rate was only 26.7%(4/15)and 26.3%(5/19),respectively.Conclusions:Immunohistochemical staining of curettage specimens before fertility preservation treatment is helpful to understand the prognosis of EC and AH patients,and the expression rate of Ki-67 is of great significance in predicting the efficacy of fertility preservation treatment.Ki-67<20%and p53-negative were more prone to disease remission,but if Ki-67<20%,the likelihood of failure to remit as scheduled was high.