Axillary Node Micrometastases: Detection and Biologic Significance

Axillary lymph node status is the single most important predictor of overall survival in patients with breast cancer. Standard histopathologic examination of regional lymph nodes relies on one microscopic section of each node to detect metastatic disease. The spectrum of metastatic disease in a lymph node ranges from complete replacement of the node by tumor to isolated nests of tumor cells in the subcapsular sinus. The clinical significance of micrometastases in axillary lymph nodes has changed over time. Micrometastases are defined by the American Joint Committee on Cancer as tumor foci less than or equal to 2 mm in greatest dimension. Retrospective studies of node-negative breast cancer patients employing intensive histopathologic examination of the axillary lymph nodes consistently show that up to a third of these patients are actually node positive. Studies published through the mid-1980s failed to show any significant effect of these micrometastases on survival. More recent studies (mid-1980s-1997) with more than 10 years of clinical follow-up have come to a different conclusion. It now appears that micrometastases are associated with a small, but statistically significant, decrease in tumor-free survival and overall survival, as compared with truly node-negative breast cancer patients. Additional slides stained with hematoxylin and eosin ("levels"), immunohistochemistry for cytokeratin proteins (found only in epithelial cells), and reverse transcriptase polymerase chain reaction for cytokeratin protein mRNA have all been used to detect micrometastases in recently published studies. The methodology utilized to detect micrometastases clearly affects the sensitivity of their detection. The current issue is the most appropriate method of detection of these small foci of tumor, given technical and cost considerations. The clinical significance of single malignant cells in the subcapsular sinus of lymph nodes, identified only by immunohistochemistry or molecular techniques, remains unclear.