Estrogen signaling in colorectal carcinoma microenvironment: expression of ER[beta]1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression

• Published in: Virchows Archiv : an international journal of pathology Vol. 454; no. 4; p. 389
• Main Authors: Tzelepi, Vassiliki, Grivas, Petros, Kefalopoulou, Zinovia, Kalofonos, Haralabos, Varakis, John N, Melachrinou, Maria, Sotiropoulou-bonikou, Georgia
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.04.2009
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-009-0740-z

Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue, mediated mainly through estrogen receptor beta (ERβ). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Expression of ERα, ERβ1, and the ER coregulators, amplified in breast cancer-1 (AIB-1) and transcriptional intermediary factor 2 (TIF-2), was evaluated in myofibroblasts of 107 colorectal carcinomas, 77 paired samples of normal mucosa, and 29 adenomas by immunohistochemistry. Double immunostaining with a-SMA was used to identify the myofibroblasts of normal tissue, adenomas, and cancer microenvironment. ERα was not expressed in stromal cells. Nuclear expression of ERβ1, AIB-1, and TIF-2 in myofibroblasts gradually increased from normal mucosa, through adenomas, to carcinomas. Cytoplasmic ERβ1 and TIF-2 expression was enhanced in carcinomas compared to normal mucosa and adenomas. Enhanced nuclear and cytoplasmic ERβ1 expression and elevated nuclear AIB-1 expression were more frequently noted in myofibroblasts of carcinomas of advanced stage. ERβ1 expression in cancer-associated myofibroblasts correlated to AIB-1 and TIF-2 expression. None of the markers correlated with patients' prognosis. Our findings imply that ERβ1-dependent (genomic and non-genomic) and ER-coregulator-dependent (AIB-1, TIF-2) signal transductions in myofibroblasts may be involved in the initiation and progression of colorectal carcinomas.