Expression profile of BRCA1 and BRCA2 genes in premenopausal Mexican women with breast cancer: clinical and immunohistochemical correlates.
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.
Loredo-Pozos
Gloria
G
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.
Chiquete
Erwin
E
Oceguera-Villanueva
Antonio
A
Panduro
Arturo
A
Siller-López
Fernando
F
Ramos-Márquez
Martha E
ME
D000328:Adult; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D024682:BRCA2 Protein / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008800:Mexico; D017697:Premenopause / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human