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Pàgina inicial > Articles > Articles publicats > Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas |
Data: | 2012 |
Resum: | 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. |
Ajuts: | Instituto de Salud Carlos III PI06-0709 Instituto de Salud Carlos III PI06/1495 Instituto de Salud Carlos III RTICCCFIS/RD06-0020-0015 |
Drets: | 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. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Publicat a: | British Journal of Cancer, Vol. 106 (03 2012) , p. 1367-1373, ISSN 1532-1827 |
7 p, 393.3 KB |