Clonality analysis of multifocal carcinoid tumours of the small intestine by X-chromosome inactivation analysis

The clonality of intestinal carcinoids and the relationship between differe nt tumour deposits of multiple intestinal carcinoids mere investigated in t his study, Six cases of multiple ileal carcinoids mere selected for analysi s and three independent carcinoid lesions from each case mere microdissecte d. Clonality of the lesions mas determined by polymerase chain reaction (PC R)based X-chromosome inactivation of the human androgen receptor gene. Four out of sh cases were heterozygous for microsatellite repeats within the an drogen receptor gene and thus informative for the study. The results showed that all 12 lesions analysed had non-random X-chromosome inactivation (mon oclonal) patterns, compared with the background normal intestinal mucosal t issues, This finding proves for the first time the monoclonal origin of hum an intestinal carcinoids, by S-chromosome inactivation analysis. More inter estingly, identical X-chromosome inactivation patterns were found in differ ent carcinoid lesions from each individual case, This evidence strongly ind icates that multiple carcinoids of the small intestine mere generated by me tastasis of a primary tumour to different locations in the intestine, rathe r than being of multiple origin. This study provides an important insight i nto the carcinogenesis of intestinal carcinoids. Copyright (C) 2000 John Wi ley & Sons, Ltd.