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This raises the question as to when clonal cell differentiation occurs during fibroid development, and does this information provide clues about possible mechanisms regulating the growth process that leads to fibroids of symptom-causing size? This study investigated the differences in the cellular composition of fibroids by immunohistochemistry (IHC). A tissue microarray (n\u2009=\u200921 hysterectomy cases) was used for the investigation of large uterine fibroids and normal myometrium. An investigation of small fibroids (\u2264 5mm) used a separate group of samples (n\u2009=\u20097 hysterectomy cases, total of n\u2009=\u200917 fibroids). A panel of cell phenotypic markers was selected based on our previous in situ investigations and included aldehyde dehydrogenase 1 (ALDH1A1) and vimentin for different fibroblast sub-populations, smooth muscle actin (SMA) as a marker for SMCs, CD31 for endothelial cells and CD45 for leucocytes. Proliferating cell nuclear antigen (PCNA) was also studied to identify proliferating cells. 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 leucocytes (measured by CD45) than adjacent myometrium, whereas small fibroids are less proliferative and have similar number of leucocytes to myometrium. Different cellular composition between fibroids of different sizes may provide important clues as to the mechanisms that drive fibroid growth.<\/jats:p>","DOI":"10.1530\/rep-16-0216","type":"journal-article","created":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T20:48:00Z","timestamp":1471294080000},"page":"467-480","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":31,"title":["Differences in the cellular composition of small versus large uterine fibroids"],"prefix":"10.1093","volume":"152","author":[{"given":"Sarah J","family":"Holdsworth-Carson","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Melbourne, Gynaecology Research Centre, Royal Women\u2019s Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Melbourne, Gynaecology Research Centre, Royal Women\u2019s Hospital, Parkville, Victoria, Australia"},{"name":"Department of Minimally Invasive Gynecologic Surgery Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Cann","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Melbourne, Gynaecology Research Centre, Royal Women\u2019s Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Bittinger","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology Royal Women\u2019s Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron J","family":"Nowell","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences Monash University, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A W","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Melbourne, Gynaecology Research Centre, Royal Women\u2019s Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,11,1]]},"reference":[{"key":"2026010712460995300_bib1","first-page":"463","article-title":"Uterine fibroids: correlations of anemia and pain to fibroid location and uterine weight","volume":"56","author":"Bachmann","year":"2011","journal-title":"Journal of Reproductive Medicine"},{"key":"2026010712460995300_bib2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.fertnstert.2010.05.011","article-title":"Short-term change in growth of uterine leiomyoma: tumor growth 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