Yang Q, Sakurai T, Mori I, Yoshimura G, Nakamura M, Nakamura Y, Suzuma T, Tamaki T, Umemura T, Kakudo K
Department of Surgery, Affiliated Kihoku Hospital, Wakayama Medical University School of Medicine, Katuragi-cho, Wakayama, Japan.
Cancer. 2001 Jul 1;92(1):54-60. doi: 10.1002/1097-0142(20010701)92:1<54::aid-cncr1291>3.0.co;2-8.
BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian carcinoma syndrome. The primary objective of the current study was to investigate the influence of BRCA1 expression on the prognoses of sporadic breast carcinomas.
A cohort of 175 Japanese women with invasive breast carcinoma who had no family history in first-degree relatives was studied. Expression of BRCA1 was determined by an immunohistochemical procedure in which the MS110 monoclonal antibody was used. Kaplan--Meier and Cox proportional regression survival analyses were used to compare negative and positive BRCA1 patients.
One hundred fifteen (65.7%) of the 175 specimens showed positive BRCA1 staining (> 10% cells were immunoreactive). During a median follow-up of 4.4 years, negative BRCA1 patients had worse disease free survival than positive BRCA1 patients (35 % vs. 7%, respectively; P < 0.0001). BRCA1 expression was significantly inversely correlated with histologic grade (P < 0.0001) but not with lymph node status or other conventional prognostic markers. In multivariate analysis using the Cox regression model, positive BRCA1 emerged as an independent prognostic indicator for disease free survival.
The results of this study suggest that BRCA1 may be a valuable marker for identifying women with sporadic breast carcinoma at high risk of developing recurrence, and who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.
BRCA1是一种肿瘤抑制基因,与遗传性乳腺癌和卵巢癌综合征相关。本研究的主要目的是探讨BRCA1表达对散发性乳腺癌预后的影响。
对175名日本浸润性乳腺癌女性患者进行队列研究,这些患者的一级亲属无家族病史。采用免疫组织化学方法,使用MS110单克隆抗体测定BRCA1的表达。采用Kaplan-Meier法和Cox比例回归生存分析比较BRCA1阴性和阳性患者。
175份标本中有115份(65.7%)BRCA1染色呈阳性(>10%的细胞具有免疫反应性)。在中位随访4.4年期间,BRCA1阴性患者的无病生存率低于BRCA1阳性患者(分别为35%和7%;P<0.0001)。BRCA1表达与组织学分级显著负相关(P<0.0001),但与淋巴结状态或其他传统预后标志物无关。在使用Cox回归模型的多变量分析中,BRCA1阳性是无病生存的独立预后指标。
本研究结果表明,BRCA1可能是一种有价值的标志物,用于识别散发性乳腺癌复发风险高的女性,这些女性可能是研究新疗法与标准辅助治疗联合应用试验的候选者。