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Bettstetter, M.* ; Berezowska, S.* ; Keller, G.* ; Walch, A.K. ; Feuchtinger, A. ; Slotta-Huspenina, J.* ; Feith, M.* ; Drecoll, E.* ; Höfler, H. ; Langer, R.*

Epidermal growth factor receptor, phosphatidylinositol-3-kinase catalytic subunit/PTEN, and KRAS/NRAS/BRAF in primary resected esophageal adenocarcinomas: Loss of PTEN is associated with worse clinical outcome.

Hum. Pathol. 44, 829-836 (2013)
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Alterations of the epidermal growth factor receptor (EGFR) can be observed in a significant subset of esophageal adenocarcinomas (EACs), and targeted therapy against EGFR may become an interesting approach for the treatment of these tumors. Mutations of KRAS, NRAS, BRAF, and phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and deregulation of PTEN expression influence the responsiveness against anti-EGFR therapy in colorectal carcinomas. We investigated the prevalence of these events in a collection of 117 primary resected EACs, correlated the findings with EGFR expression and amplification, and determined their clinicopathologic impact. KRAS mutations were detected in 4 (3%) of 117 tumors (3× G12D and 1 G12V mutation). One tumor had a PIK3CA E545K mutation. Neither NRAS nor BRAF mutations were detected. Sixteen (14%) of 117 cases were negative for PTEN expression, determined by immunohistochemistry. Loss of PTEN was observed predominantly in advanced tumor stages (P = .004). There was no association between PTEN and EGFR status. Loss of PTEN was associated with shorter overall and disease-free survival (P < .001 each) and also an independent prognostic factor in multivariate analysis (P = .015). EGFR status had no prognostic impact in this case collection. In summary, loss of PTEN can be detected in a significant subset of EAC and is associated with an aggressive phenotype. Therefore, PTEN may be useful as a prognostic biomarker. In contrast, mutations of RAS/RAF/PIK3CA appear only very rarely, if at all, in EAC. A possible predictive role of PTEN in anti-EGFR treatment warrants further investigations, whereas determination of RAS/RAF/PIK3CA mutations may only have a minor impact in this context.
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Publication type Article: Journal article
Document type Scientific Article
Keywords EGFR; PTEN; PIK3CA; KRAS; NRAS; BRAF; Esophagus adenocarcinoma; Metastatic Colorectal-cancer ; Cetuximab Plus Oxaliplatin/leucovorin/5-fluorouracil ; Internistische Onkologie Aio ; In-situ Hybridization ; Esophagogastric Junction ; Barretts-esophagus ; Phase-ii ; Prognostic-significance ; Kras Mutations ; Colon-cancer
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