Estrogen Receptor β as a Prognostic Marker of Tumor Progression in Colorectal Cancer with Familial Adenomatous Polyposis and Sporadic Polyps

Abstract

The incidence of colorectal cancer (CRC) is lower in women than in men, and sex steroids can be considered contributing factors because oral contraception usage and estrogen replacement therapy are associated with decreased risk. Conversely, colorectal polyp development in familial adenomatous polyposis (FAP) begins during puberty. The objectives were to evaluate the relationship between the expression of these hormone receptors and adenoma-carcinoma progression, CRC stage and overall survival. We studied 120 A.C. Camargo Cancer Center patients diagnosed with either FAP-associated or spontaneous adenomatous polyps or CRC to determine the immunohistochemical expression levels of estrogen receptor (ER)-α, ER-β and the progesterone and androgen receptors (480 analyses). The ER-β expression levels differed between the groups: the group with FAP polyps had lower ER-β expression than that of the sporadic polyp group. With transformation of the sporadic polyps to cancer, there was a considerable decrease in ER-β expression (from 90% with strong expression to 80% with absent or weak expression) (p < 0.001). The ER-β expression was lower in T3/T4 tumors than in T1/T2 tumors (p = 0.015). The 5-year overall survival of CRC patients positively expressing ER-β exceeded that of patients without detectable expression levels (74.8% vs. 44.3%, respectively; p = 0.035). There was no significant expression of the androgen or progesterone receptor or ER-α among the groups. Differences in ER-β expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.

Hormone Replacement Therapy in Cancer Survivors – Review of the Literature

“…Estrogen receptor overexpression, however, has not only been found in the well-known estrogen dependent tumour types, such as breast, endometrial and ovarian cancer. Altered estrogen and / or progesterone receptor expression has been documented for example in thyroid cancer [12][13][14][15], Hodgkin's lymphoma [16][17][18], B-cell malignancies [19,20], brain tumours [21][22][23][24][25], prolactinoma [26,27], melanoma [28][29][30][31], lung cancer [32,33], colorectal cancer [34][35][36], gastric cancer [37] and liver cancer [38,39].…”

Estrogen and Progesterone Expression in Colorectal Carcinoma: A Clinicopathological Study

“…CRC is a major health problem with high mortality rate globally (Haraldsdottir et al, 2014). Sex steroids have been suggested to influence CRC carcinogenesis (Stevanato Filho et al, 2018) and their possible role has been demonstrated in multiple epidemiologic studies (Williams et al, 2016). However, their role as prognostic factors in colon cancer still controversial.…”

“…Supported by a number of clinical and laboratory observations; CRC incidence tends to be lower in females than in males suggested that ovarian steroids may be contributing factors. Also, oral contraception and hormonal replacement therapy are associated with reduced CRC risk (Stevanato Filho et al, 2018). Presence of estrogens was associated with lower risk of CRC as shown by In-vitro and epidemiological studies (Weyant et al, 2001;Foster, 2013) and The Women's Health Initiative findings supported that postmenopausal women treated with hormone replacement therapy had lower colon cancer incidence (Rossouw et al, 2002).…”

“…Estrogen receptor beta (ERβ) is by far the predominant isoform in the colon mucosa (Campbell-Thompson et al, 2001;Konstantinopoulos et al, 2003;Wong et al, 2005) and its expression is lost during the progression of colon cancer (Foley et al, 2000;Wada-Hiraike et al, 2006). Also, Elevated ER beta expression was associated with a better prognosis in patients with CRC as shown in recent studies (Stevanato Filho et al, 2018, Topi et al, 2017. Also, the presence of both ER and progesterone (PR) expression was associated with lower proliferation and more apoptosis of colon cancer, probably through ER receptor beta activation (Sasso et al, 2019).…”

PathME: pathway based multi-modal sparse autoencoders for clustering of patient-level multi-omics data

“…ER signaling including ER-α and ER-β is implicated in CRC pathogenesis and progression and it is considered as a potential preventive and therapeutic target [55]. Estrogen Receptor 2 (ESR2), the gene encoding ER-β, is considered as a prognostic marker [56]. Another important pathway related to the CRC adenoma to carcinoma transition is the Ras pathway [57].…”