Nonrandom chromosomal numerical abnormality as a new molecular cytogenetic tumor marker--a retrospective study of 60 gastric cancer cases.

Chromosomal numerical abnormality (CNA) is one of the distinct characteristics of human cancers, though the mechanisms and tumor specificity of this phenomenon have not been adequately analyzed. Recently, we developed a new sensitive fluorescence in situ hybridization (FISH) method that involves short-term microwave (MW) treatment for hybridization. In this study, we applied this modified FISH technique to investigate the CNA of 60 gastric cancer cases with a panel of 18 chromosome-specific alpha-satellite probes (for chromosome 1-4, 6-12, 15-18, 20, X, and Y) and region-specific probes (c-myc, p53, and Her-2/neu) to enumerate the respective chromosome numbers in interphase nuclei of formalin-fixed paraffin-embedded sections. The numerical aberrations of chromosome 1, 3, 8, 17, 20, and X were frequent regardless of histologic types, whereas aberrations of chromosomes 10, 15, and 18 occurred less frequently (p<0.001). From a histopathological standpoint, the mucocellular type of carcinoma had stable CNA in comparison with the tubular type of carcinoma (21.7+/-9.63% vs. 58.3+/-12.32%, p<0.001) and, of note, there was less extensive CNA in female cases. A dramatic difference in patient outcome was detected according to the involvement of chromosomes 3, 10, 11, 12, 17, and Y; cases with CNA of these chromosomes had a worse prognosis (p<0.001). A two-step analysis of the CNA of 6 chromosomes and locus specific gene abnormalities successfully divided gastric cancer cases into those with a good outcome and those with a poor outcome. This analysis allows one to more accurately predict prognosis than by using a simple classification based on conventional clinicopathological diagnosis.