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.

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.

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

The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis.

Therkildsen C ，Bergmann TK ，Henrichsen-Schnack T ，Ladelund S ，Nilbert M ... -  《-》

Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers.

Lee SY ，Kim MJ ，Jin G ，Yoo SS ，Park JY ，Choi JE ，Jeon HS ，Cho S ，Lee EB ，Cha SI ，Park TI ，Kim CH ，Jung TH ，Park JY ... -  《-》

Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group 《-》

Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer.

Ludovini V ，Bianconi F ，Pistola L ，Chiari R ，Minotti V ，Colella R ，Giuffrida D ，Tofanetti FR ，Siggillino A ，Flacco A ，Baldelli E ，Iacono D ，Mameli MG ，Cavaliere A ，Crinò L ... -  《-》