Undifferentiated Cell Markers in the Endometrium of Women with Endometriosis

Endometriosis is a benign chronic disease characterized by the presence of tissue resembling the endometrium outside the uterine cavity. The etiology of endometriosis appears to be polygenic and multifactorial, but the exact pathogenic mechanisms are still unclear. In recent years, adult stem cells have been identified in various human tissues including the endometrium, and these cells may be associated with the pathogenesis of proliferative gynecological diseases such as endometriosis. The identification of adult stem/progenitor cells (SPCs) in tissues is highly complex and can be inferred from the identification of undifferentiated cell markers. This study investigated the expression of undifferentiated markers Musashi-1, Oct-4, and c-kit in eutopic endometria of patients with and without endometriosis and endometriotic lesions using immunohistochemistry (IHC) on a non-biotin polymer detection system. Four tissue specimens of normal endometrium and six samples of eutopic and ectopic endometria from patients with endometriosis were evaluated. Categorical variables were analyzed by the chi-square test and immunoreactivity scores (IRS) were tested using the Kruskal-Wallis test. Musashi-1 protein expression presented as cytoplasmic or nuclear staining, Oct-4 staining was predominantly nuclear, and c-kit protein expression presented as transmembrane and cytoplasmic staining. The three markers were positively immunostained in all endometrial compartments evaluated (glandular epithelium, stroma, and endothelium). The percentage of Musashi-1 expressing cells was significantly higher in the endothelium of patients with endometriosis (p < 0.05). Musashi-1 and c-kit demonstrated staining of cell groups, which may correspond to stem cell clusters. Overall, the three markers demonstrated high staining intensity and percentage. c-kit expression was significantly higher in glandular epithelium than in the stromal compartment (p < 0.05), and stromal IRS was significantly higher in eutopic endometrial samples from patients with endometriosis (p < 0.05). In conclusion, putative endometrial SPCs may play a role in the physiopathology of endometriosis, not only in the origin of ectopic implants, but also through involvement in neoangiogenesis.

Keywords: Surface antigens. Adult stem cells. Endometrium. Endometriosis. Physiopathology.