Expression of HOXB4 in endometrial tissues from women with or without endometriosis

Endometriosis is a benign gynecological disease that affects up to 10% of women of reproductive age; however, the pathogenesis of endometriosis remains poorly understood. HOX genes encode transcription factors that play roles in regulating cell proliferation, differentiation, angiogenesis, adhesion and motility in adult tissues – key features of endometriosis. The aim of this study was to examine the localization of HOXB4, via immunohistochemistry (IHC), in both eutopic (EE) and ectopic endometrial tissues (deep infiltrating endometriosis (DIE) and endometriomas (Eoma)) from women with endometriosis and compare it to endometrial tissue from women with no history of endometriosis (EC). The localization of HOXB4 in these tissues was determined via immunohistochemistry (IHC) with a monoclonal HOXB4 antibody, where immunoreactivity was assessed by Histoscore (H-Score) method. HOXB4 protein was present in the endometrial glandular epithelial cells only. HOXB4 immunoreactivity in EC was significantly higher in the proliferative phase than in the secretory phase of the menstrual cycle; however, this difference was lost among the diseased groups (EE, Eoma and DIE). Interestingly, HOXB4 expression was significantly lower in the DIE lesions compared to matched eutopic endometrium and endometrioma /DIE lesions. After normalizing HOXB4 mRNA levels to endometrial epithelial cell content, consistent with IHC results, HOXB4 mRNA levels were significantly lower in the DIE groups when compared to EC and Eoma. On the whole, HOXB4 expression is reduced in DIE, but not endometrioma, and may be dysregulated in ectopic implants. During the menstrual cycle, the expression of HOXB4 in endometrial glandular epithelial cells is higher in the proliferative phase than the secretory phase in the normal eutopic endometrium. We here report for the first time the expression of HOXB4 localization and immunoreactivity not only in the normal eutopic endometrium but also in both eutopic and ectopic endometrial tissues in women with endometriosis.