Molecular characterization of human adenomyosis

Abstract

Adenomyosis is a common gynaecological disorder characterized by the abnormal growth of endometrium into the myometrium and myometrial hypertrophy/hyperplasia. Uterine fibroids are benign neoplasms of the myometrium, and they represent a diagnostic pitfall for adenomyosis. In this study, we have used the genome-wide Affymetrix U133 Plus 2.0 microarray platform to compare the gene expression patterns of adenomyosis, uterine fibroids, normal endometrium and myometrium. Unsupervised principal component analysis (PCA) revealed that these four tissue types could be segregated from one another solely based on their gene expression profiles. Analysis of variance (ANOVA), followed by Tukey means separation test, significance analysis of microarrays (SAM) and 2-fold change threshold, identified 7415 probe sets as differentially expressed among the four groups of samples. Supervised cluster analysis based on these probe sets clustered adenomyosis most closely with endometrium and uterine fibroids with myometrium, consistent with the anatomic origin of these two diseases. The Tukey means separation post hoc testing found 2073 probe sets altered between adenomyosis and normal endometrium or myometrium, and 2327 probe sets altered in expression when comparing uterine fibroids with myometrium. Using Ingenuity Pathways Analysis (IPA), we found 9 highly significant functional networks in adenomyosis and 10 in uterine fibroids. Notably, the top network in both cases was associated with functions implicated in cancer and cell death. Finally, we compared the gene expression profiles of adenomyosis and uterine fibroids and identified 471 differentially expressed probe sets that may represent potential biomarkers for the differential diagnosis of these diseases.

Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator

“…5). When adenomyosis or uterine fibroid-associated genes were analyzed by IPA, no immune response-associated pathways were detected (11).…”

Adenomyosis and Endometrial Cancer: Literature Review

“…Both adenomyosis and type 1 endometrial cancer have been linked to sex steroid action. The gene expression profile suggests a role of cancer, cell death and cell cycle networks in adenomyosis [2]. More recently, the expression of microRNA-17 was shown to be significantly increased and mRNA of Phosphatase and Tensin Homolog (PTEN-mRNA) to be reduced in adenomyosis [3].…”

Pathogenesis and malignant transformation of adenomyosis (Review)

“…Ovarian steroids are key regulators of a number of these processes. Activation of several of these pathways and their downstream targeted genes are involved in regulating a wide variety of processes that regulate ovarian steroid synthesis, immune response, metabolism, matrix accumulation, angiogenesis and local inflammatory response (10). Although the full implications of the differentially expressed genes are not yet completely understood, adenomyosis samples clustered closely with endometrium samples (10).…”

“…Myometrial smooth muscle dysfunction also develops as a primary or steroid hormone-induced defect in adenomyosis (8). Following invagination of stromal cells, invasion of glandular cells, abnormal growth and differentiation, these cells are subsequently surrounded by hypertrophic and hyperplastic myometrium (9,10). These data suggest that adenomyosis might be caused by defects in the formation of the inner myometrial layer of the uterus (8).…”

“…Abnormalities of inflammatory response, cytokine/chemokine expression, protease activation, autophagy, immunosuppressive microenvironment and epigenetic regulation may be present in adenomyosis. Numerous genes, including CXCL10, calbindin D-28K, prostaglandinrelated factors [such as prostaglandin E receptor 3 (subtype EP3) and prostaglandin synthase], COX-2 and cancer-and cell death-related genes are differentially expressed in adenomyosis (10,33). CXCL10 modulates adhesion molecule expression through stimulation of monocytes and natural killer and T-cell migration.…”