Malignant potential and cytogenetic characteristics of occult disseminatedtumor cells in esophageal cancer

Although micrometastatic cancer cells in lymph nodes can be detected by mon oclonal antibodies against epithelial or tumor-associated antigens, it rema ins unclear whether these cells are precursors of overt metastases or shedd ed tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characterist ics of such micrometastases. In lymph nodes classified as tumor free by con ventional histopathological staging, tumor cells were identified with monoc lonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R-0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells i n "node-negative" (pN(0)) patients. To assess the biology of Ber-EP4-positi ve cells, we established tumor cell lines from an immunohistochemically pos itive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberration s shared between both cell lines, whereas an insertion of chromosome 13 mat erial in the short arm of chromosome 1 was only observed in micrometastatic cells, The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our d ata provide first direct evidence for the malignant potential of micrometas tatic cancer cells.