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

Abstract

The clonality of intestinal carcinoids and the relationship between different tumour deposits of multiple intestinal carcinoids were investigated in this study. Six cases of multiple ileal carcinoids were selected for analysis and three independent carcinoid lesions from each case were microdissected. Clonality of the lesions was determined by polymerase chain reaction (PCR)-based X-chromosome inactivation of the human androgen receptor gene. Four out of six cases were heterozygous for microsatellite repeats within the androgen receptor gene and thus informative for the study. The results showed that all 12 lesions analysed had non-random X-chromosome inactivation (monoclonal) patterns, compared with the background normal intestinal mucosal tissues. This finding proves for the first time the monoclonal origin of human intestinal carcinoids, by X-chromosome inactivation analysis. More interestingly, identical X-chromosome inactivation patterns were found in different carcinoid lesions from each individual case. This evidence strongly indicates that multiple carcinoids of the small intestine were generated by metastasis of a primary tumour to different locations in the intestine, rather than being of multiple origin. This study provides an important insight into the carcinogenesis of intestinal carcinoids.