title: Molecular alterations of EGFR and PTEN in prostate cancer: association with high-grade and advanced-stage carcinomas.
abstract: Prostate cancer is the second cause of cancer-related death in men of the Western world. The potential prognostic role of the combined alterations in EGFR and PTEN in prostate cancer is not well established. It was the aim of the study to investigate this role. Prevalence of EGFR and PTEN somatic mutations, EGFR amplification and EGFR protein expression were investigated in a series of prostate adenocarcinomas, classified according to the current Gleason grading system. Mutational analysis revealed eight EGFR and three PTEN mutations in 98 (8%) and 92 (3%) prostate adenocarcinomas, respectively. The combined prevalence of EGFR-PTEN mutations was 11%. EGFR overexpression was present in 31% of adenocarcinomas, with a marginally significant difference (P=0.068) between Gleason grade < or =7 adenocarcinomas and Gleason grade > or =8 and metastatic adenocarcinomas. Four cases (4 of 31; 13%) had an EGFR gene gain due to chromosome 7 polysomy. In 35% of adenocarcinomas we found some type of EGFR-PTEN alteration, with a tendency to be associated with advanced-stage prostate adenocarcinomas (P=0.04). The IVS18+19 polymorphism was also associated with more advanced prostate adenocarcinomas. This is the first study reporting mutations of EGFR and PTEN in the same series of prostate adenocarcinomas. Protein overexpression is the most frequent EGFR abnormality. Mutations in EGFR and PTEN genes are a minor event, although prostate cancer represents the third neoplasm in which the EGFR gene mutations are more prevalent. Alterations in the EGFR-PTEN signaling pathway are present in a third of prostate adenocarcinomas, particularly affecting the more advanced cases.
authors.affiliation: Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Muga
authors.forename: Silvia
authors.initials: S
authors.lastname: Hernández
authors.forename: Laia
authors.initials: L
authors.lastname: Agell
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.forename: Nuria
authors.initials: N
authors.lastname: Juanpere
authors.forename: Marta
authors.initials: M
authors.lastname: Lorenzo
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000235:genetics
chemical_list: D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase