Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T^sub 1^ human breast carcinomas

The overexpression of Bcl-2, an anti-apoptotic oncogene, identifies human T1 breast cancer patients who have an increased risk of lymph-node metastasis. We examined in these patients (n = 142) whether the c-Myc oncogene influences metastatic progression in conjunction or not with Bcl-2 expression and the loss of apoptosis in tumors. The association between Bcl-2 and lymph-node metastasis was only significant when c-Myc was concomitantly expressed (chi2 test, p = 0.008). Moreover, very large associations (pOR = 6.4) between c-Myc and lymph-node metastasis were observed among Bcl-2 positive tumors and tumors with loss of apoptosis (pOR = 8.4). In contrast, the metastatic advantage linked to Bcl-2 was decreased (pOR = 2) when c-Myc was not coexpressed. It is concluded that the synergism between Bcl-2 and c-Myc oncogenes may promote metastasis in breast tumors, linked to loss of apoptosis.