CHROMOSOMAL IMBALANCES IN PRIMARY AND METASTATIC PANCREATIC-CARCINOMAAS DETECTED BY INTERPHASE CYTOGENETICS - BASIC FINDINGS AND CLINICAL ASPECTS

To date, cytogenetic studies on pancreatic carcinoma are rare, and lit tle is known about the frequency of cytogenetic aberrations in primary carcinomas compared with metastatic tumour cells. We therefore evalua ted the frequency of chromosomal aberrations in 12 primary pancreatic carcinomas and in effusion specimens from 25 patients with pancreatic cancer by using interphase fluorescence in situ hybridization (FISH) a nd a panel of four centromeric probes. Hyperdiploidy and chromosomal i mbalances, predominantly affecting chromosome 8, were a constant findi ng in metastatic effusion cells, whereas concordant gain of chromosome s or relative loss of chromosome 18 characterized primary pancreatic c arcinomas. The potential role of oncogenes located on chromosome 8 for pancreatic cancer progression was further investigated by double-hybr idization studies of aneuploid effusion cells with a probe to 8q24 (MY C) and a centromeric probe to chromosome 8, which demonstrated amplifi cation of the MYC oncogene in two of ten cases (20%). Finally, a poten tial application of basic findings in the clinical setting was tested by searching for micrometastatic cells in effusions from pancreatic ca ncer patients primarily negative by FISH. Two-colour FISH in combinati on with extensive screening (>10 000 nuclei) seems to be a useful tool to unequivocally identify micrometastatic cells by demonstrating hype rdiploidy and intranuclear chromosomal heterogeneity.