2024-03-29T10:33:55Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1431302017-02-02T01:56:36Zcom_10261_11773com_10261_1col_10261_11774
Prognostic relevance of estrogen receptor-alpha Ser167 phosphorylation in stage II-III colon cancer patients
López-Calderero, Iker
Carnero, Amancio
Astudillo, Aurora
Palacios Calvo, José
Chaves-Conde, Manuel
Benavent, Marta
Limón, María L.
García-Carbonero, Rocío
Junta de Andalucía
Instituto de Salud Carlos III
Colon cancer
Prognosis
Immunohistochemistry
Estrogen receptor
Survival
Biomarkers
Tissue microarray
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-ERαSer167 (pERαSer167) expression was assessed by immunohistochemistry in 218 CRC paraffin-embedded tumor samples. A high pERαSer167 expression was more commonly observed in women, older patients, and patients with high baseline glucose levels. This higher pERαSer167 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 pERαSer167 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 pERαSer167, respectively). Multivariate analysis confirmed that pERαSer167 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.
The authors would like to thank the donors and the Andalusian Public Health System Biobank Network (ISCIII-Red de Biobancos RD09/0076/00085) for the human tumor specimens provided for this study.
Peer Reviewed
2017-01-30T10:19:27Z
2017-01-30T10:19:27Z
2014-12
2017-01-30T10:19:27Z
artículo
http://purl.org/coar/resource_type/c_6501
issn: 0046-8177
Human Pathology 45(12): 2437–2446 (2014)
http://hdl.handle.net/10261/143130
10.1016/j.humpath.2014.08.008
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100011011
http://doi.org/10.1016/j.humpath.2014.08.008
Sí
none
Elsevier