DNA microarray analysis of gene expression in eutopic endometrium from patients with deep endometriosis using laser capture microdissection

Objective: To investigate differentially expressed genes in epithelial, and stromal cells of eutopic endometrium from patients with deep endometriosis and women with normal pelvic cavities using laser capture microdissection and complementary DNA microarrays. Design: Prospective study. Setting: University hospital. Patient(s): Patients with deep endometriosis and fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. Intervention(s): Endometrial tissue biopsies during the late proliferative phase and early, mid-, and late secretory phases. Main Outcome Measure(s): Genes that were regulated with a change greater than threefold were selected as differentially expressed genes. Validation was performed with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Result(s): Microarray analysis identified up-regulation during the late secretory phase (patients with endometriosis vs. controls) of several genes in two important signaling pathways: RAS/RAF/MAPK and PI3K. This included the genes RON, SOS, 14-3-3 protein eta, and uPAR in epithelial cells and KSR and PI3K p85 regulatory subunit alpha in stromal cells; real-time RT-PCR analysis validated up-regulation of all six genes. Conclusion(s): The RAS/RAF/MAPK and PI3K pathways may be involved in initial development of endometriosis.