6th ESACP Congress, Heidelberg, April 7-11, 1999

A152
FLUORESCENCE IN SITU HYBRIDIZATION (FISH) ANALYSIS OF 8Q24, 13Q14, 7Q31 AND 20Q13 IN TISSUE SECTIONS SHOW GREAT HETEROGENEITY IN GASTRIC CANCERS
Weiss MM, Van Grieken NCT, Meijer GA, Hermsen M, Craanen ME, Meuwissen SGM, Baak JPA, Kuipers EJ

Free University Hospital, Depts of Gastroenterology and Pathology, Amsterdam, the Netherlands

Background: Little is known about the genetic aberrations leading to H. pylori induced gastric cancer. We therefore performed comparative genomic hybridization (CGH) on gastric carcinomas (Van Grieken et al., Gastroenterology 14:A695, 1998). However, CGH does not give specific information on the distribution of copy number changes in tumor cells. Aim : To investigate heterogeneity of chromosomal copy number changes in gastric cancers by FISH on tissue sections. Methods : FISH was performed on small frozen tissue sections of 5 gastric cancers with centromeric (cen 22) and locus specific probes (8q24: c-myc, 17p: p53, 13q14: Rb, 7q31, 20q13) (guided by the CGH results previously obtained in the same tumors). Samples were analyzed by interactive spot counting in 100 tumor cell nuclei and 100 non-tumor cell nuclei, the ratio of these counts (T/N ratio) was taken as an indication of chromosomal copy number. Results: The experiments yielded clear hybridization signals combined with good conservation of tissue morphology. Within tumors carrying a gain detected by CGH, considerable heterogeneity of copy number changes was seen with FISH (mean SD=1.8); in a case with a high level gain by CGH, with FISH copy numbers ranged from 0 to 20 (SD=3.7). In general, CGH and FISH results showed a good correlation. Conclusions: The high level of intra tumor heterogeneity detected by FISH in tissue sections provides new insights on chromosomal copy number changes in gastric cancer.