534P - Prognostic impact of phospho-ER-alpha (PER-α) in surgically resected colon cancer

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Colon Cancer
Translational Research
Presenter Iker Calderero
Authors I.L. Calderero1, A.C. Moya2, A.A. Gonzalez3, A.C. Carranza4, M.C. Conde1, S. Molina-Pinelo2, M.D.P. Herrera2, M.L.L. Miron1, P.E. Garcia1, R. Garcia-Carbonero1
  • 1Oncology Service, Hospital Virgen del Rocio, 41013 - Seville/ES
  • 2Laboratorio De Biologia Molecular Del Cancer, Instituto de Biomedicina de Sevilla, Seville/ES
  • 3Departamento De Anatomía Patológica, Hospital central de Asturias, Oviedo/ES
  • 4Pathology Department, Hospitales Universitarios Virgen del Rocio, Seville/ES

Abstract

Background

Preclinical models and randomized clinical trials suggest a protective role for estrogens against colorectal cancer (CRC). ER-� is the prevalent estrogen receptor in normal colonic mucosa, while its expression is significantly reduced in CRC. An increased ER-α/� ratio has been documented in colon carcinomas and this is associated with increased proliferation and decreased apoptosis. The aim of our study was to evaluate the expression of activated ER-α and its prognostic implications in a series of patients with surgically resected stage II-III CRC.

Methods

Phosphorylated ER-α [Ser167] expression was evaluated by immunohistochemistry (IHC) in tissue microarrays (TMA) of 218 CRC paraffin-embedded tumor samples. A pER-α score was calculated for each sample according to staining intensity and proportion of stained cells assessed by two pathologists blinded to the clinical data. Univariate and multivariate analyses were performed to assess the correlation of pER-α score with clinicopathological features and survival.

Results

pER-α staining was negative in 39 tumors (18%), 1+ in 164(75%), 2+ in 11(5%), and unavailable in 4(2%). Half of the samples had positive staining in >10% of tumor cells. A high pER-α score was more common in women (female:56% vs male:45%; p = 0.07), older patients (>65years:56% vs <65years:40%; p = 0.02), and patients with high baseline glucose levels (Glu > 120mg/dl:66% vs <120mg/dl: 45%; p = 0.01). This higher pER-α expression was associated with a strong trend to a decreased 5-year disease free interval (DFI) (66% vs 78%; p = 0.07) and a lower overall survival (OS)(65% vs 73%; p = 0.46). A high pER-α score had a significant (p < 0.05) negative impact on DFI in women (85% vs 60%), young (82% vs 61%), non-diabetic (85% vs 66%) and stage II patients (86% vs 72%)[low vs high pER-α, respectively]. Multivariate analysis confirmed pER-α score was a significant prognostic factor for both DFI and OS, independent of gender, age, glucose levels, tumor stage, bowel obstruction/perforation and adjuvant chemotherapy.

Conclusions

ER-α is expressed in a high proportion of patients with CRC and is associated with a worse prognosis, particularly in women, young, non-diabetic and stage II patients.

Disclosure

All authors have declared no conflicts of interest.