title: Prognostic relevance of estrogen receptor-α Ser167 phosphorylation in stage II-III colon cancer patients.
abstract: Preclinical and clinical data suggest a protective role for estrogens on colon cancer (CRC) risk. estrogen receptor (ER) β is the prevalent ER in normal colonic mucosa, whereas its expression is significantly reduced in CRC. An increased ERα/β ratio has been documented in colon carcinomas and is associated with increased proliferation and decreased apoptosis. The aim of our study was to evaluate the expression of activated ERα and its prognostic implications in patients with stage II-III CRC. Phospho-ERα(Ser167) (pERα(Ser167)) expression was assessed by immunohistochemistry in 218 CRC paraffin-embedded tumor samples. A high pERα(Ser167) expression was more commonly observed in women, older patients, and patients with high baseline glucose levels. This higher pERα(Ser167) expression was associated with decreased 5-year disease-free interval (DFI; 66% versus 78%, P = .07) and overall survival (65% versus 73%, P = .46). The negative impact of high pERα(Ser167) expression on DFI was particularly significant (P < .05) in women (85% versus 60%), young (82% versus 61%), nondiabetic (85% versus 66%), and stage II patients (86% versus 72% and low versus high pERα(Ser167), respectively). Multivariate analysis confirmed that pERα(Ser167) score was a significant prognostic factor for both DFI and overall survival, independent of sex, age, glucose levels, tumor stage, bowel obstruction/perforation, or adjuvant chemotherapy. These findings illustrate the relevance of estrogen pathways in colon cancer biology and may provide novel therapeutic avenues to be explored in this context.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain; Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain.
authors.forename: Iker
authors.initials: I
authors.lastname: López-Calderero
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain.
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.affiliation: Department of Pathology, Hospital Central de Asturias, Asturias, 33006, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.affiliation: Department of Pathology, Hospital Universitario Virgen del Rocío, Seville, 41013, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Palacios
authors.affiliation: Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Chaves
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain; Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Benavent
authors.affiliation: Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Limón
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain; Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Seville, 41013, Spain. Electronic address: rgcarbonero@gmail.com.
authors.forename: Rocio
authors.initials: R
authors.lastname: Garcia-Carbonero
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D012737:Sex Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha
keywords: Biomarkers; Colon cancer; Estrogen receptor; Immunohistochemistry; Prognosis; Survival; Tissue microarray