Significance of Loss of Heterozygosity in Predicting Axillary Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast

Invasive ductal carcinoma (IDC) of breast metastatic to axillary lymph node (ALN) is a critical factor in determining stage and is a strong predictor of disease prognosis and survival. We studied ALN metastasis using a combined histopathologic/molecular approach to gain insights into the pathobiology implications. Fourteen patients with IDC with positive ALN and 19 with negative ALN were retrieved. Analysis of 17 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was carried out in DNA isolated from primary tumors and metastatic tumors. ALN metastasis correlated with fractional mutation rate of primary and ALN metastatic tumors, primary tumor size, and nuclear grade, and did not correlate with expression of estrogen receptor, progesterone receptor, and Her2/neu. Loss of heterozygosity (LOH) detected at 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q12, 21q22, and 22q13 may play an important role in the development and aggressiveness of IDC, and LOHs at 1p34-36, 17p13, and 22q13 may play an important role in metastasis. None of the LOHs were shared by all the tumors, suggesting that IDC develops through various pathways that have unique and personalized patterns of mutational changes, although they share similar morphology. Detection of LOH in IDC is not only useful in studying oncogenesis, but also predicting aggressiveness and ALN metastasis.