p53凋亡刺激蛋白家族成员在浸润性乳腺癌中的表达及其意义

Expression of apoptosis-stimulating protein of p53 family members in invasive breast cancer and its prognostic significance

目的研究p53凋亡刺激蛋白(ASPP)家族成员在浸润性乳腺癌中的表达,并探讨其与p53表达状态、乳腺癌分子分型及预后的关系。方法收集2005年1月至2010年4月解放军第九八九医院收治的155例浸润性乳腺癌患者组织标本进行回顾性分析。采用免疫组织化学方法检测组织标本中ASPP1、ASPP2、P53凋亡刺激蛋白抑制因子(iASPP)、p53、ER、PR、HER-2和Ki67的表达,并用χ^2检验分析ASPP家族成员表达与乳腺癌分子分型和p53状态的关系,采用Kaplan-Meier生存分析方法评价ASPP家族成员表达与患者预后的关系。结果155例乳腺癌组织中,ASPP1阳性率为13.5%(21/155),ASPP2阳性率为97.4%(151/155),iASPP阳性率为61.3%(95/155)。表达野生型p53者33例,突变型p53者122例,p53的突变率为78.7%(122/155)。ASPP家族成员的表达在野生型p53组与突变型p53组间差异无统计学意义(ASPP1:χ^2<0.001,P=0.987;ASPP2:χ^2=1.110,P=0.579;iASPP:χ^2=0.244,P=0.621)。luminal A型44例,luminal B型66例,basal-like型18例,HER-2过表达型27例,ASPP家族成员的表达在不同分子分型乳腺癌组间差异无统计学意义(ASPP1:χ^2=2.325,P=0.508;ASPP2:χ^2=1.657,P=0.642;iASPP:χ^2=0.815,P=0.846)。随访时间2~108个月,中位随访时间66个月,患者3年总生存率为84.5%(131/155),5年OS率为79.4%(123/155)。ASPP1、ASPP2和iASPP表达阳性组与阴性组相比,患者5年OS率的差异均无统计学意义(ASPP1:χ^2=3.790,P=0.050;ASPP2:χ^2=0.040,P=0.927;iASPP:χ^2=1.253,P=0.263)。结论ASPP家族成员在浸润性乳腺癌中的表达与P53突变、乳腺癌分子分型以及乳腺癌患者预后均无关。

Objective To explore the expression of apoptosis-stimulating protein of p53(ASPP)family members in invasive breast cancer and their relationship with p53 expression,molecular subtype and prognosis of patients.Methods The tissue samples from 155 invasive breast cancer patients in the Department of Pathology,No.989 Hospital of PLA from January 2005 to April 2010 were analyzed retrospectively.The expression of ASPP family members(ASPP1,ASPP2,iASPP),p53,ER,PR,HER-2 and Ki67 in breast cancer tissue samples was detected by immunohistochemistry.The relationship between the expression of ASPP family members and different molecular subtypes or p53 expression were analyzed byχ^2 test,and the Kaplan-Meier method was used to analyze the relationship between expression of ASPP family members and patient survival.Results In the invasive breast cancer tissue samples of 155 cases,the positive rate of ASPP1 was 13.5%(21/155),ASPP297.4%(151/155),and iASPP 61.3%(95/155).There were 33 cases of wild-type p53 expression and 122 cases of p53 mutation expression,so the mutation rate of p53 was 78.7%(122/155).There was no significant difference in the expression of ASPP family members between the wild-type p53 expression group and p53 mutation group(ASPP1:χ^2<0.001,P=0.987;ASPP2:χ^2=1.110,P=0.579;iASPP:χ^2=0.244,P=0.621).There were 44 patients with luminal A subtype breast cancer,66 luminal B,18 basal-like and 27 HER-2 over-expression in all 155 patients,suggesting no significant difference in the expression of ASPP family members across different subtypes(ASPP1:χ^2=2.325,P=0.508;ASPP2:χ^2=1.657,P=0.642;iASPP:χ^2=0.815,P=0.846).The patients were followed up for 2-108 months,median 66 months.The 3-year survival rate was 84.5%(131/155)and 5-year survival rate was 79.4%(123/155).There was no significant difference between ASPP1/ASPP2/iASPP positive group and negative group in the 5-year survival(ASPP1:χ^2=3.790,P=0.050;ASPP2:χ^2=0.040,P=0.927;iASPP:χ^2=1.253,P=0.263).Conclusions The expression of ASPP family members in invasive breast cancer is not related to p53 mutation,molecular subtype and survival.