Intratumor heterogeneity of centromere numerical abnormality in multiple primary gastric cancers: application of fluorescence in situ hybridization with intermittent microwave irradiation on paraffin-embedded tissue.

Our recent success in retrieving distinct fluorescence signals in response to centromere specific probing of paraffin-embedded tissues after intermittent microwave (MW) treatment provided the opportunity to analyze chromosome numbers or centromere abnormality in situ in human tumors in various clinicopathological settings. In this study, centromere numerical abnormality (CNA) was investigated by fluorescence in situ hybridization (FISH) in a case of multiple gastric cancer having intratumor histological heterogeneity. The different profiles as determined using a total of 20 specific probes on 4 multifocal lesions in the stomach confirmed the multi-clonality of these tumors. FISH with probes specific for chromosomes 10, 11, 16 and 18 revealed intratumor heterogeneity of the CNA, which corresponded to the histological heterogeneity. Our report clearly demonstrates, for the first time, intratumor heterogeneity of CNA and its association with the histological picture, and substantiates the applicability of the MW-assisted FISH protocol to paraffin-embedded pathological specimens.