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墨西哥绝经前乳腺癌女性中BRCA1和BRCA2基因的表达谱:临床及免疫组化相关性

Expression profile of BRCA1 and BRCA2 genes in premenopausal Mexican women with breast cancer: clinical and immunohistochemical correlates.

作者信息

Loredo-Pozos Gloria, Chiquete Erwin, Oceguera-Villanueva Antonio, Panduro Arturo, Siller-López Fernando, Ramos-Márquez Martha E

机构信息

Instituto de Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Colonia Independencia, Guadalajara, Jalisco C.P. 44340, Mexico.

出版信息

Med Oncol. 2009;26(3):269-75. doi: 10.1007/s12032-008-9114-7. Epub 2008 Nov 15.

Abstract

Low BRCA1 gene expression is associated with increased invasiveness and influences the response of breast carcinoma (BC) to chemotherapeutics. However, expression of BRCA1 and BRCA2 genes has not been completely characterized in premenopausal BC. We analyzed the clinical and immunohistochemical correlates of BRCA1 and BRCA2 expression in young BC women. We studied 62 women (mean age 38.8 years) who developed BC before the age of 45 years. BRCA1 and BRCA2 mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and that of HER-2 and p53 proteins by immunohistochemistry. Body mass index (BMI) > or = 27 (52%) and a declared family history of BC (26%) were the main risk factors. Ductal infiltrative adenocarcinoma was found in 86% of the cases (tumor size >5 cm in 48%). Disease stages I-IV occurred in 2, 40, 55, and 3%, respectively (73% implicating lymph nodes). Women aged < or = 35 years (24%) had more family history of cervical cancer, stage III/IV disease, HER-2 positivity, and lower BRCA1 expression than older women (P < 0.05). BRCA1 and BRCA2 expression correlated in healthy, but not in tumor tissues (TT). Neither BRCA1 nor BRCA2 expression was associated with tumor histology, differentiation, nodal metastasis or p53 and HER-2 expression. After multivariate analysis, only disease stage explained BRCA1 mRNA levels in the lowest quartile. Premenopausal BC has aggressive clinical and molecular characteristics. Low BRCA1 mRNA expression is associated mainly with younger ages and advanced clinical stage of premenopausal BC. BRCA2 expression is not associated with disease severity in young BC women.

摘要

BRCA1基因低表达与侵袭性增加相关,并影响乳腺癌(BC)对化疗药物的反应。然而,BRCA1和BRCA2基因在绝经前BC中的表达尚未完全明确。我们分析了年轻BC女性中BRCA1和BRCA2表达的临床及免疫组化相关性。我们研究了62名在45岁之前患BC的女性(平均年龄38.8岁)。通过逆转录聚合酶链反应(RT-PCR)评估BRCA1和BRCA2 mRNA表达,通过免疫组化评估HER-2和p53蛋白表达。体重指数(BMI)≥27(52%)和有明确的BC家族史(26%)是主要危险因素。86%的病例为导管浸润性腺癌(48%肿瘤大小>5 cm)。疾病分期I-IV分别占2%、40%、55%和3%(73%累及淋巴结)。年龄≤35岁的女性(24%)比年龄较大的女性有更多的宫颈癌家族史、III/IV期疾病、HER-2阳性以及更低的BRCA1表达(P<0.05)。BRCA1和BRCA2在健康组织中表达相关,但在肿瘤组织(TT)中不相关。BRCA1和BRCA2表达均与肿瘤组织学、分化、淋巴结转移或p53及HER-2表达无关。多因素分析后,仅疾病分期可解释最低四分位数中BRCA1 mRNA水平。绝经前BC具有侵袭性的临床和分子特征。BRCA1 mRNA低表达主要与绝经前BC患者年龄较小及临床晚期相关。BRCA2表达与年轻BC女性的疾病严重程度无关。

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