BRCA1 gene expression in breast cancer: a correlative study between real-time RT-PCR and immunohistochemistry.
Breast cancer is a major cause of cancer-related mortality in women. There are major discrepancies concerning the usefulness of various antibodies in detecting breast cancer susceptibility gene 1 (BRCA1) protein and its subcellular localization. The aim of the present study was to determine the specificity and sensitivity of immunohistochemistry (IHC) as a screening method for demonstrating BRCA1 expression. BRCA1 gene expression in archival paraffin-embedded breast cancer tissues was studied simultaneously at the protein and mRNA levels, and the two findings were compared. Forty-eight archival paraffin-embedded breast cancer tissues were studied for BRCA1 gene expression at protein level by IHC using four different antibodies against different BRCA1 epitopes and at mRNA level using real-time RT-PCR. BRCA1 mRNA expression was reduced or absent in 79% of the samples, and this finding correlated significantly with loss of BRCA1 protein expression in 83% of breast cancer tissues using one BRCA1 antibody studied (AB-1, against N-terminus epitope). The specificity of this antibody was 91.3%, and its sensitivity was 66.6%. There was no significant correlation between BRCA1 mRNA and protein expression as demonstrated by the remaining three antibodies. Antibody 8F7 had the highest sensitivity of 100%, but its specificity was 30.4% if mRNA levels were considered as the reference standard.
Al-Mulla
Fahd
F
Department of Pathology, Molecular Pathology Laboratory, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. fahd@al-mulla.org
Abdulrahman
Mahera
M
Varadharaj
Govindarajulu
G
Akhter
Nadeem
N
Anim
Jehoram T
JT
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016612:Paraffin Embedding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D019313:BRCA1 Protein