dc.contributor.author |
Gallardo, Alberto |
dc.contributor.author |
Lerma Puertas, Enrique |
dc.contributor.author |
Escuin i Borràs, Daniel |
dc.contributor.author |
Tibau Martorell, Ariadna |
dc.contributor.author |
Muñoz, J. |
dc.contributor.author |
Ojeda, Belén |
dc.contributor.author |
Barnadas i Molins, Agustí |
dc.contributor.author |
Adrover, E. |
dc.contributor.author |
Sánchez-Tejada, L. |
dc.contributor.author |
Giner, D. |
dc.contributor.author |
Ortiz-Martínez, F. |
dc.contributor.author |
Peiró, G.. |
dc.contributor.author |
Universitat Autònoma de Barcelona |
dc.date |
2012 |
dc.identifier |
https://ddd.uab.cat/record/184827 |
dc.identifier |
urn:10.1038/bjc.2012.85 |
dc.identifier |
urn:oai:ddd.uab.cat:184827 |
dc.identifier |
urn:pmid:22454081 |
dc.identifier |
urn:pmcid:PMC3326683 |
dc.identifier |
urn:pmc-uid:3326683 |
dc.identifier |
urn:articleid:15321827v106p1367 |
dc.identifier |
urn:recercauab:ARE-74149 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/11ebcfbf-3193-409d-b365-f73b65e9e829 |
dc.identifier |
urn:scopus_id:84859627290 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:3326683 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Instituto de Salud Carlos III PI06-0709 |
dc.relation |
Instituto de Salud Carlos III PI06/1495 |
dc.relation |
Instituto de Salud Carlos III RTICCCFIS/RD06-0020-0015 |
dc.relation |
British Journal of Cancer ; Vol. 106 (03 2012), p. 1367-1373 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
dc.title |
Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas |
dc.type |
Article |
dc.description.abstract |
Trastuzumab resistance hampers its well-known efficacy to control HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this mechanism is still not definitively confirmed. We selected 155 patients treated with trastuzumab after development of metastasis or as adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR, epidermal growth factor 1-receptor (EGFR), α -insulin-like growth factor 1-receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110 α, pAkt, pBad, pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN, and PTEN promoter hypermethylation. We found 46% ER/PR-positive tumours, overexpression of EGFR (15%), α -IGF1R (25%), p110 α (19%), pAkt (28%), pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17% and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with α -IGF1R or pBad overexpressing tumours presented shorter progression-free survival (PFS) (all P ⩽0.043). Also, p110 α and mTOR overexpression, liver and brain relapses implied poor overall survival (OS) (all P ⩽0.041). In patients with metastatic disease, decreased PFS correlated with p110 α expression (P =0.024), whereas for OS were the presence of vascular invasion and EGFR expression (P ⩽0.019; Cox analysis). Our results support that trastuzumab resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast carcinomas. |