Gene expression profiling of multiple leiomyomata uteri and matched normal tissue from a single patient.

ABSTRACT

OBJECTIVE: To identify differentially expressed genes between fibroid and adjacent normal myometrium in an identical hormonal and genetic background. DESIGN: Array analysis of three leiomyomata and matched adjacent normal myometrium in a single patient. SETTING: University of Colorado Hospital. PATIENT(S) A single female undergoing medically indicated hysterectomy for symptomatic fibroids. INTERVENTIONS(S) mRNA isolation and microarray analysis, reverse-transcriptase polymerase chain reaction, Western blotting, and immunohistochemistry. MAIN OUTCOME MEASURE(S) Changes in mRNA and protein levels in leiomyomata and matched normal myometrium. RESULT(S) Expression of 197 genes was increased and 619 decreased significantly by at least twofold, in leiomyomata relative to normal myometrium. Expression profiles between tumors were similar and normal myometrial samples showed minimal variation. Changes in, and variation of, expression of selected genes were confirmed in additional normal and leiomyoma samples from multiple patients. CONCLUSION(S) Analysis of multiple tumors from a single patient confirmed changes in expression of genes described in previous, apparently disparate, studies, and identified novel targets. Gene expression profiles in leiomyomata are consistent with increased activation of mitogenic pathways and inhibition of apoptosis. Down-regulation of genes implicated in invasion and metastasis, of cancers, was observed in fibroids. This expression pattern may underlie the benign nature of uterine leiomyomata and may aid in the differential diagnosis of leiomyosarcoma.