mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30%, of node-neg ative patients relapse within five years, suggesting that current methods a re inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay . An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study f irst investigated the expression of seven mRNA markers, CEA, CK19, c-Met, m ammaglobin, MUC-1, beta1 --> GalNAc-T and p97, selected on the basis of the ir previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA an d CEA mRNA were not expressed in normal nodes. All of the other markers sho wed a band of expression in ITV 55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be d etected in 15/20 (75%) and 19/20 (95%,,) primary breast carcinomas, respect ively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histologica l evidence of metastatic disease. Ninety-seven per cent of the patients wit h histologically involved nodes showed expression of mammaglobin mRNA, wher eas CEA mRNA was expressed in 79%, of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicatin g the presence of metastases not detected by routine histological examinati on of one lymph node section. These results show that both mammaglobin RT-P CR and CEA RT-PCR are useful tools for the detection of breast cancer metas tases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis o f occult metastases in nearly one-third of cases. Copyright (C) 2001 John W iley & Sons, Ltd.