Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: Comparison with nonmetastatic Barrett's adenocarcinoma

Lymph node metastasis is one of the strongest negative prognostic factors f or patients with Barretts adenocarcinoma (BCA). However, despite the import ance of the metastatic process in BCA, the molecular basis of it remains po orly understood. To search for cytogenetic events associated with metastasi s in regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their lymph node metastases and compared them with 18 nonmetastatic BCA . In metastatic primary BCA, we observed significantly more DNA gains on 3q (P = .013), 17q (P = .019), and 22q (P = .021) compared with nonmetastatic primary BCA. No statistically significant correlation could be observed be tween DNA copy number changes and the histopathologic stage, grade, or surv ival (P > .05). The most frequent alteration observed only in lymph node me tastases but not in the related primary tumor was loss of 2q (5 of 8). Coam plification of 7p and chromosome 17 was found in 6 of 8 lymph node metastas es. A comparison of DNA copy number changes between primary tumors and thei r corresponding metastases indicated a high degree of genetic heterogeneity . Fluorescence in situ hybridization analysis demonstrated the involvement of the Her-2/neu gene in primary BCA and its related lymph node metastases. Each of the investigated primary tumors and related lymph node metastases also showed striking heterogeneity with respect to Her-2/neu, with several areas displaying different levels of amplification. In summary, our data in dicate that DNA copy number changes on 2q, 3q, 7p, 17q, and 22q may be invo lved in the metastatic process in BCA. Furthermore, the striking genetic he terogeneity that we found between primary BCA and its lymph node metastases may underlie BCA's poor responsiveness to therapy and could help explain w hy prognostic biomarkers measured exclusively in primary tumors give an inc omplete view of the biologic potential of BCA.