摘要
目的探讨乳腺癌2型易感基因(BRCA2)致病突变的前列腺癌临床病理特征及其与预后的相关性。方法收集2014年6月至2021年8月在四川大学华西医院确诊并行基因检测的249例前列腺癌的临床病理资料。回顾性分析组织学形态,总结临床病理特征,并随访患者生存情况。结果249例前列腺癌患者基因检测结果显示有73例(29.3%)检出DNA损伤修复基因(DNA damage repair gene,DRG)致病突变,涉及18个DRG的胚系或体系致病突变。其中BRCA2致病突变率最高(22/249,8.8%),另检出51例其他DRG致病突变,其余176例无DRG致病突变。22例BRCA2致病突变患者年龄48~91岁,中位年龄67岁,包括14例胚系突变(14/249,5.6%)和8例体系突变(8/249,3.2%)。17例(77.3%)有远处转移,其中16例为骨转移,1例为多部位转移;13例(59.1%)为去势抵抗性前列腺癌。组织学形态以经典的腺泡腺癌为主,其中16例(72.7%)伴有导管内癌成分,6例(27.3%)局灶伴神经内分泌表型,11例(50.0%)查见神经或血管侵犯,8例(36.4%)查见前列腺外累及。19例(86.4%)患者Gleason评分≥8分。相比BRCA2体系致病突变、其他DRG致病突变和无DRG致病突变的病例,前列腺导管内癌成分在BRCA2胚系致病突变的病例中更常见(P=0.002)。本组病例223例获得随访资料,总随访时间为189个月,中位总生存期132.3个月。DRG致病突变的患者比无DRG致病突变的患者预后差,总生存期更短(P=0.040);BRCA2胚系致病突变患者与BRCA2体系致病突变、其他DRG致病突变、无DRG致病突变患者的总生存期差异无统计学意义(P=0.216)。结论BRCA2致病突变常见于Gleason高分级、临床高分期和去势抵抗性前列腺癌。BRCA2胚系致病突变病例具有独特的组织学形态,常伴有前列腺导管内癌成分。本组病例中,DRG致病突变的患者比无DRG致病突变的患者预后差,总生存期更短;但BRCA2致病突变与患者的预后无明显相关性。
Objective To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations,and the association between BRCA2 pathogenic mutation and clinicopathological characteristics.Patient survivals were also examined.Methods Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University,Chengdu,China from June 2014 to August 2021 were collected.A retrospective analysis of histopathological morphology,clinicopathological characteristics,and patient survivals was conducted.Results The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene(DRG)in 73 cases(73/249,29.3%),including 22 cases(8.8%)with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG.Among the 22 patients with BRCA2 pathogenic mutation,14 patients(5.6%)harbored germline mutations and 8 patients(3.2%)somatic mutations.Their ages ranged from 48 to 91 years,with a median of 67 years.Seventeen patients(77.3%)had distant metastasis,including 16 cases with bone metastasis and 1 case with multiple metastases.Thirteen patients(59.1%)were castration-resistant prostate cancer.The histological type was mainly classical prostatic acinar adenocarcinoma,including 16 cases(72.7%)with intraductal carcinoma of the prostate(IDC-P).Six cases(27.3%)showed focal neuroendocrine differentiation.Perineural/vascular invasion and extraprostatic extension were seen in 11 cases(50.0%)and 8 cases(36.4%),respectively.The Gleason scores of 19 patients(86.4%)were≥8.IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation,other DRG pathogenic mutation or no-DRG pathogenic mutation(P=0.002).With a total follow-up time of 189 months,the median overall survival(OS)was 132.3 months.Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation(P=0.040).The OS of patients with BRCA2 germline pathogenic mutation did n
作者
王铎淏
尹文莲
潘秀懿
张孟尼
聂玲
陈雪芹
曾浩
周桥
陈铌
Wang Duohao;Yin Wenlian;Pan Xiuyi;Zhang Mengni;Nie Ling;Chen Xueqin;Zeng Hao;Zhou Qiao;Chen Ni(Department of Pathology,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Urology,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2024年第8期789-796,共8页
Chinese Journal of Pathology
基金
国家自然科学基金(82273047,82273073,82203280)
四川省科技厅基金(24SYSX0223,2022YFS0305)。
