Genetic and epigenetic alterations in sentinel lymph nodes metastatic lesions compared to their corresponding primary breast tumors

The accumulation of genetic and epigenetic changes plays a pivotal role in tumor development and progression. In this study, we investigated these changes using comparative genomic hybridization and bisulfite polymerase chain reaction analysis for CpG island hypermethylation of the following genes: TP16, THBS2, E-Cadherin (ECAD), RARbeta2, MINT1, MINT2, and MINT31 in six paired primary breast tumors and their matched sentinel lymph nodes (SLN). The most frequent chromosomal alterations observed were the following: losses of 6q13similar toq23 and 13q13similar toq32 and gains of 9q31similar toqter, 11p15similar toq21, 12q23similar toqter, and 20q12similar toqter. Gain of 6p21similar topter was observed in the SLN but in none of the primary tumors. Overall, 71% (30/42) of the methylation measurements were identical between the primary tumors and the SLN. Of the six cases, two showed no differences between the primary tumors and SLN, one tumor with 4 of 7 genes hypermethylated in the primary tumor showed loss of all four hypermethylation events in the SLN, and the remaining three tumors showed loss of one methylation event and simultaneous gain of one to two methylation changes in the SLN. This is the first study reporting genetic and epigenetic alterations in breast sentinel lymph nodes compared to their corresponding primary tumors. Characterization of such alterations may lead to identification of initial events associated with the metastatic dissemination process. (C) 2003 Elsevier Inc. All rights reserved.