A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays

Abstract

This article will discuss some recent insights based on our microarray studies that have emphasized the role the extracellular matrix, transforming growth factor beta, and collagen structure in fibroid formation. These studies led to appreciation of molecular similarities between fibroids and keloids. Collectively, these observations suggest a model of fibroid development based on an abnormal response to tissue repair, resulting in disordered healing and formation of an altered extracellular matrix.

Figure 1

Cumulative incidence of hysterectomy, by race. Y-axis: Incidence of hysterectomy. X-axis: Age at time of surgery. Data are from analysis of surgical outcomes by Dr Evan Myers (modified and reprinted from with permission “Management of Uterine Fibroids,” AHRQ Publication No 01-E052).

Figure 2

Electron microscopy of A, uterine fibroid and B, normal myometrium. Original magnification ×64,000. Note the disordered, irregularly aligned collagen fibrils in A, compared with the tightly packed and closely spaced collagen fibrils in B, normal uterine ECM.

Figure 3

Model of abnormal wound healing in fibroids. Tissue repair is a tightly regulated process with progressive differentiation of cells secreting the ECM, and production of an ECM that is capable of bearing stress. Collagen remodeling is a key feature of repair and TGF-β plays a critical role in production of the fibrosis associated with healing. Myofibroblasts are highly differentiated cells that undergo apoptosis at completion of the repair, but arrest in differentiation before the final stages of differentiation may result in continued secretion of collagen and excessive fibrosis.