Introduction: Uterine fibroids are clonally derived from a single cell, but despite being monoclonal, the cellular phenotypes that make up uterine fibroids are heterogeneous consisting predominantly of smooth muscle cells (SMC) and fibroblasts. This raises the question as to when during fibroid development clonal cell differentiation occurs, and does this information provide clues about possible mechanisms regulating the growth process that leads to fibroids of symptom-causing size?
Methods: This study investigated fibroids by immunohistochemistry (IHC) for differences in cellular composition. A tissue microarray (n = 21 hysterectomy cases) was used for the investigation of large uterine fibroids and normal myometrium. An investigation of small fibroids (<5mm) used a separate group of samples (n = 7 hysterectomy cases, total of n=17 fibroids). A panel of cell phenotypic markers were selected based on our previous in situ investigations and included: aldehyde dehydrogenase 1 (ALDH1) and vimentin for different fibroblast sub-populations, smooth muscle actin (SMA) as a marker for SMCs, CD31 for endothelial cells and CD45 for leukocytes. Proliferating cell nuclear antigen (PCNA) was also studied to identify proliferating cells.
Results: The cellular composition of small fibroids differs significantly from large fibroids. Small fibroids are more cellular (increased cells / mm2) than large fibroids, have more blood vessels, and also have a higher ratio of SMC to fibroblasts than large fibroids. Large fibroids have more cell proliferation (measured by PCNA) and fewer leukocytes (measured by CD45) than adjacent myometrium, while small fibroids are less proliferative and have similar leukocyte numbers to myometrium.
Conclusion: The different cellular compositions we have indentified between fibroids of different sizes may provide important clues as to the mechanisms that drive fibroid growth. Cellular heterogeneity may also help to explain differences in the growth patterns and symptomology of individual uterine fibroids.