Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics: basic findings and clinical aspects

Abstract

Summary To date, cytogenetic studies on pancreatic carcinoma are rare, and little is known about the frequency of cytogenetic aberrations in primary carcinomas compared with metastatic tumour cells. We therefore evaluated 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) and a panel of four centromeric probes. Hyperdiploidy and chromosomal imbalances, predominantly affecting chromosome 8, were a constant finding in metastatic effusion cells, whereas concordant gain of chromosomes or relative loss of chromosome 18 characterized primary pancreatic carcinomas. The potential role of oncogenes located on chromosome 8 for pancreatic cancer progression was further investigated by double-hybridization studies of aneuploid effusion cells with a probe to 8q24 (MYC) and a centromeric probe to chromosome 8, which demonstrated amplification of the MYC oncogene in two of ten cases (20%). Finally, a potential application of basic findings in the clinical setting was tested by searching for micrometastatic cells in effusions from pancreatic cancer patients primarily negative by FISH. Two-colour FISH in combination with extensive screening (>10 000 nuclei) seems to be a useful tool to unequivocally identify micrometastatic cells by demonstrating hyperdiploidy and intranuclear chromosomal heterogeneity.

c-MYC Activation in Primary and Metastatic Ductal Adenocarcinoma of the Pancreas: Incidence, Mechanisms, and Clinical Significance

“…In contrast, an immunohistochemical study failed to detect overexpression of c-MYC in 20 pancreatic cancers (13). Recently, amplification of the c-MYC oncogene was identified by FISH in 2 of 10 metastatic pancreatic effusion cells (14) and in 4 of 7 human xenografted pancreatic tumors (5). However, all studies pertaining to c-MYC in pancreatic cancer are based on small tumor numbers and appear therefore of limited validity.…”

“…To date, little is known about genomic and proteomic changes affecting c-MYC in pancreatic cancer. The available data are controversial and show a varying incidence of c-MYC deregulation in the small number of pancreatic cancers analyzed (5,(12)(13)(14). Therefore, further and more detailed investigations to assess the biological significance and prognostic value of c-MYC activation in pancreatic carcinogenesis are demanded.…”

Stepwise Progression of Centrosome Defects Associated with Local Tumor Growth and Metastatic Process of Human Pancreatic Carcinoma Cells Transplanted Orthotopically into Nude Mice

“…Cytogenetic analyses of primary and metastatic pancreatic carcinomas have shown that chromosome abnormalities occur at higher frequencies in metastatic tumors than in primary tumors (Zojer et al, 1998). Alterations in the numbers and structures of chromosomes reflect defective mitosis, including unequal distribution of chromosomes to daughter cells.…”

“…In fact, pancreatic cancer is frequently characterized by numerical and structural aberrations in chromosomes, a hallmark of genetic instability (Griffin et al, 1995;Hahn et al, 1995). Cytogenetic analyses of primary and metastatic pancreatic carcinomas have shown that chromosomal abnormalities occur at higher frequencies in metastatic tumors than in primary tumors (Zojer et al, 1998). Furthermore, pancreatic carcinomas xenografted in nude mice acquire a higher degree of genetic aberration during tumor dissemination (Reyes et al, 1996).…”

Fluorescence In Situ Hybridization to Visualize Genetic Abnormalities in Interphase Cells of Acinar Cell Carcinoma, Ductal Adenocarcinoma, and Islet Cell Carcinoma of the Pancreas

“…An assortment of genetic procedures have been attempted to investigate pancreatic cancer, including family history studies, 1 conventional cytogenetic techniques, 10 interphase FISH, [11][12][13] comparative genomic hybridization, 14 RNA expression analyses, 15, 16 and evaluation of sequence variations. 17 These studies implicate a variety of point mutations and chromosomal anomalies in most, if not all, patients with pancreatic cancer.…”