Estrogen receptor beta expression correlates with proliferation in desmoid tumors

Abstract

Background and objectives Estrogen receptor signaling and cyclin D1 have a major role in tumor cell proliferation in breast cancer. Desmoid tumors are rare neoplasms that may respond to endocrine treatment. The present study aimed to investigate the expression levels and the clinical relevance of estrogen receptor beta (ERβ) and cyclin D1 in desmoid tumors. Methods This study consists of 83 patients with a surgically treated desmoid tumor. ERβ and cyclin D1 expression was examined by immunohistochemistry in tissue microarrays. Cyclin A and Ki67 were studied in our previous work. Results Median ERβ expression was 10.8%. ERβ expression correlated with expression of the proliferation antigens Ki67 (rp = 0.35, P = 0.003), cyclin D1 (rp = 0.34, P = 0.004), and cyclin A (rp = 0.34, P = 0.004). ERβ immunoexpression showed a trend towards predictive impact for recurrence as a continuous variable. Further explorative analysis indicated that very high ERβ expression was related to high risk of relapse (hazard ratio [HR] 2.6; P = 0.02).Median cyclin D1 expression was 15.6%. High cyclin D1 expression was associated with high Ki67 and cyclin A expression. Cyclin D1 was not associated with time to recurrence. Conclusions ERβ and cyclin D1 immunopositivity correlated with high proliferation in desmoid tumors. High ERβ expression might be predictive for postoperative recurrence.

The role of estrogen receptor beta in breast cancer

“…Alternations in estrogenic signaling pathways, as well as ERβ expression, have been discussed in the context of physiological and pathological processes, such as maintenance of the bone marrow microenvironment [ 11 ], neuronal-mediated contractions of the gastrointestinal tract [ 12 ], recovery of reproductive system injury [ 13 ], anxiolytic effects [ 14 ], and diseases such as Parkinson’s disease [ 15 ], endometriosis [ 16 ], myocardial infarction [ 17 ] and type 2 diabetes [ 18 ]. Moreover, ERβ has been shown to participate in the pathological process of various cancers, including uterine leiomyomas [ 19 ], colorectal cancer [ 20 ], desmoid tumors [ 21 ], prostate cancer [ 22 ] and duct carcinoma [ 23 ].…”

Molecular Pathogenesis of Sporadic Desmoid Tumours and Its Implications for Novel Therapies: A Systematised Narrative Review

“…Cyclin D1 and c-Myc signalling is commonly deregulated in tumourigenesis due to their promotional effects on cell proliferation by enhancing the G1 to S-phase transition of the cell cycle [ 34 , 35 ]. Cyclin D1 was overexpressed in at least 40% of DTF cases [ 26 , 27 , 29 , 36 ]. Two studies found a significant correlation between β-catenin nuclear expression and cyclin D1 overexpression (Fisher’s exact test, p = 0.029; Fisher’s exact test, p = 0.034, respectively) [ 27 , 29 ].…”

“…Furthermore, three studies demonstrated significantly higher CCND1 gene expression in the mutated CTNNB1 group compared with the wild-type group ( χ 2 test, p = 0.038; Mann–Whitney U test, p = 0.019; Mann–Whitney U test, p = 0.0120, respectively) [ 26 , 29 , 31 ]. Saito et al and Santti et al demonstrated significant cellular proliferative activity in DTF cases with cyclin D1 overexpression via a proliferating cell nuclear antigen-labelling index (Fisher’s exact test, p = 0.004) and Ki-67 ( r = 0.40, p = 0.001), respectively [ 27 , 36 ]. These findings suggest aberrant Wnt/β-catenin signalling may exert its proliferative effects through the overexpression of positive cell-cycle regulatory proteins.…”

Immunohistochemical evaluation of potential molecular targets of desmoid-type fibromatosis

“…Santti et al [24] have found a trend in very high ERβ expression to predict a higher risk of relapse. In our recurrent cases primary biopsy samples demonstrated high range ERβ positivity, which decreased in the rebiopsy samples even to a complete loss of expression.…”