Distinctive proliferative phase differences in gene expression in human myometrium and leiomyomata

Abstract

Objective: To gain a comprehensive view of the gene expression and regulation involved in uterine leiomyomata and matched normal myometrium using oligonucleotide microarray-based hybridization analysis.

Design: Retrospective analyses of tissue obtained in a prospective randomized clinical study.

Setting: Academic institution.

Patient(s): Seven patients with leiomyomata scheduled for surgery during the proliferative phase.

Interventions(s): Seven paired samples of leiomyomata and adjacent myometrium were obtained from patients undergoing hysterectomy.

Main outcome measure(s): The total RNA extracted from leiomyomata and myometrium was used for gene expression profiling of 6800 human genes using high-density oligonucleotide microarrays. In addition, reverse transcriptase-semiquantitative polymerase chain reaction and immunohistochemistry were used to validate tumor-specific gene expression.

Result(s): A comparison of expression patterns in each paired sample revealed 68 genes significantly up- or down-regulated in each paired tissue sample, of which 23 genes showed increased expression and 45 showed decreased expression in leiomyomata compared with normal myometrium. Cluster analysis supported the relevance of these candidate genes for distinguishing between normal myometrium and leiomyomata biologic activity.

Conclusion(s): Expression profiling of uterine leiomyomata using high-density oligonucleotide microarrays yields signature patterns that reflect the distinctive differences between normal human myometrium and leiomyomata during the proliferative phase. These observations suggest that a number of genes are involved in the tumorigenesis of leiomyomata.