Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression

Pierre P. Massion, Peter M. Taflan, Yu Shyr, S. M.Jamshedur Rahman, Pinar Yildiz, Bashar Shakthour, Mary E. Edgerton, Matthew Ninan, Jeremiah J. Andersen, Adriana L. Gonzalez

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118 Citations (Scopus)

Abstract

Signaling through the phosphatidylinositol 3-kinase (PI3-kinase) pathway has been associated with lung tumorigenesis. We examined the association between gene copy number of the PI3-kinase catalytic subunit α (PIK3CA) and phosphorylated Akt expression in invasive and preinvasive lung cancers. We sought to determine at what stage of tumor development gene copy number increase or phosphorylated Akt overexpression might affect tumor development. We assessed PIK3CA gene copy number by fluorescence in situ hybridization and expression of phosphorylated Akt by immunohistochemistry in 242 invasive and 43 preinvasive lung cancers and correlated our findings with clinical outcome. The PIK3CA was amplified in 70% of squamous carcinomas, 38% of large cell carcinomas, 19% of adenocarcinomas, and 67% of small cell lung cancers. Phosphorylated Akt overexpression was frequently observed, and strongly so in 12 to 17% of lung cancers depending on nuclear or cytoplasmic localization. Neither PIK3CA gene copy number nor phosphorylated Akt protein expression had prognostic significance. In preinvasive lesions, amplification of the PIK3CA and overexpression of phosphorylated Akt were associated with severe dysplasia and each other. These observations suggest frequent and early involvement of the PI3-kinase pathway in lung cancer.

Original languageEnglish
Pages (from-to)1088-1094
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume170
Issue number10
DOIs
Publication statusPublished - 2004 Nov 15

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Massion, P. P., Taflan, P. M., Shyr, Y., Rahman, S. M. J., Yildiz, P., Shakthour, B., Edgerton, M. E., Ninan, M., Andersen, J. J., & Gonzalez, A. L. (2004). Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression. American Journal of Respiratory and Critical Care Medicine, 170(10), 1088-1094. https://doi.org/10.1164/rccm.200404-487OC