Detection of MAGE-A3 in breast cancer patients' sentinel lymph nodes.
The detection of occult metastatic breast cancer cells by RT-PCR is limited by the poor specificity of most tumour mRNA markers. MAGE-A3 is a highly specific tumour mRNA marker that is not expressed in non-cancer cells. This study assesses MAGE-A3 mRNA as a molecular marker for the detection of tumour cells in the sentinel lymph nodes (SLN) of breast cancer patients. Serial frozen sections of SLN (n = 121) were obtained from 77 AJCC (American Joint Committee on Cancer) Stage I-IIIA breast cancer patients. MAGE-A3 mRNA analysis of SLN was performed by RT-PCR and Southern blot analysis. Tumour cells were detected in 48 of 121 (40%) SLN from 77 patients by H&E or IHC staining, and 35 of 77 (45%) patients, overall, had histopathologically (H&E and/or IHC) positive SLN. Among histopathologically negative SLN, 28 of 73 (38%) SLN were MAGE-A3 mRNA positive by RT-PCR. Overall, 41 of 77 (53%) patients and 50 of 121 (41%) SLN were positive for MAGE-A3. MAGE-A3 mRNA expression in the SLN occurred more frequently with infiltrating lobular carcinoma (P < 0.001) than with infiltrating ductal carcinoma, adding further evidence of possible phenotypic differences between these 2 subtypes of breast cancer. Due to its high specificity, MAGE-A3 mRNA is a potentially useful marker for detecting breast cancer cells in the SLN. One half of breast tumours expressed MAGE-A3 mRNA, which has important potential implications for antigen-specific targeted immunotherapy.
Wascher
R A
RA
Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA 90404, USA.
Bostick
P J
PJ
Huynh
K T
KT
Turner
R
R
Qi
K
K
Giuliano
A E
AE
Hoon
D S
DS
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000235:genetics; D009363:Neoplasm Proteins; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D017931:DNA Primers; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins