Prognostic Value of Bone Marrow Micrometastasis Detected by N

Abstract

PURPOSE: Breast cancers frequently undergo distant metastasis during the early phase, on which the survival of patients is greatly dependent. It has been suggested that the occurrence of micrometastasis relates with other prognostic features of breast cancer, such as lymph node metastasis and the presence of vascular invasion. The aim of this study was to examine the presence of keratin-19 and mammaglobin mRNA in bone marrow aspirates obtained from breast cancer patients, and their possible correlation with tumor staging and disease free survival. METHODS: Bone marrow samples were obtained from 254 breast cancer patients at the time of surgery. We separated the mononuclear fraction from the samples and carried out nested reverse transcriptase polymerase chain reaction for the detection of keratin-19 and mammaglobin mRNA using two different pairs of primers. We also studied the possible correlations between the tumor size, nodal involvement, stage, and distant metastasis. RESULTS: Seventy-five of the 254 samples were studied for cytokeratin 19 and the others for cytokeratin and mammaglobin. The median follow-up time was 21.1 months. Sixty-five (26%) of the 254 samples were cytokeratin 19 positive and 25 (14.3%) of the 175 were mammaglobin positive. Eight cases (12.3%) in the cytokeratin positive group showed a recurrent disease in distant organs. Whereas, six (3.2%) out of 185 cytokeratin negative patients had distant recurrences. Mammaglobin positivity was not correlated with distant metastasis. The stage, nodal status, and estrogen receptor were independent of bone marrow micrometastasis. CONCLUSION: Bone marrow micrometastasis, detected by nested RT-PCR for cytokeratin 19, could be a useful predictive marker for the distant metastasis of breast cancer.