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Zusammenfassung: <jats:title>Abstract</jats:title><jats:p>We investigated the status of the PI 3‐kinase/AKT/PTEN signaling pathway in a series of 117 head and neck squamous cell carcinomas (HNSCC) in a search for molecular alterations in genes/proteins with potential prognostic value. For this purpose, <jats:italic>PIK3CA</jats:italic> and <jats:italic>AKT2</jats:italic> gene amplification was assessed by multiplex and Quantitative Real‐Time PCR. Protein expression of AKT, p‐AKT, p110α and PTEN was determined by Western blot. <jats:italic>PTEN</jats:italic> allelic loss was evaluated by microsatellite analysis. <jats:italic>PTEN</jats:italic>‐exon 5 was screened for point mutations by PCR‐SSCP. Homozygous deletions were determined by multiplex PCR. <jats:italic>PIK3CA</jats:italic> gene was amplified in 43/117 (37%) fresh tumor samples, a frequency that did not differ from that found in archival premalignant tissues: 15/38 (39%); 12/40 (30%) fresh tumors harbored <jats:italic>AKT2</jats:italic> gene amplification. AKT was found activated in 6/36 (17%) fresh tumor samples, when compared to their normal tissue counterparts. Of these 6 cases, 1 showed p110α overexpression and 5 displayed PTEN protein downregulation. Neither allelic loss (found in 11/77 informative cases) nor point mutations or homozygous deletions accounted for the reduced PTEN protein expression observed in our tumor series. The histologically normal mucosa of 4 patients displayed some of the molecular alterations analyzed. Dysregulation of the PI 3‐K/AKT/PTEN pathway might contribute to early HNSCC tumorigenesis and might constitute a potential clinical target. Overall, 17/36 (47%) cases showed at least 1 of the molecular alterations studied here, which makes the PI 3‐kinase‐initiated signaling pathway one of the most frequently altered in HNSCC. © 2004 Wiley‐Liss, Inc.</jats:p>
Umfang: 242-248
ISSN: 0020-7136
1097-0215
DOI: 10.1002/ijc.20711