Massion Pierre P, Taflan Peter M, Shyr Yu, Rahman S M Jamshedur, Yildiz Pinar, Shakthour Bashar, Edgerton Mary E, Ninan Matthew, Andersen Jeremiah J, Gonzalez Adriana L
Department of Medicine, Biostatistics Shared Resource, the Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-6838, USA.
Am J Respir Crit Care Med. 2004 Nov 15;170(10):1088-94. doi: 10.1164/rccm.200404-487OC. Epub 2004 Aug 18.
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 alpha (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.
通过磷脂酰肌醇3激酶（PI3激酶）途径的信号传导与肺癌发生有关。我们研究了PI3激酶催化亚基α（PIK3CA）的基因拷贝数与浸润性和浸润前肺癌中磷酸化Akt表达之间的关联。我们试图确定在肿瘤发展的哪个阶段基因拷贝数增加或磷酸化Akt过表达可能影响肿瘤发展。我们通过荧光原位杂交评估PIK3CA基因拷贝数，并通过免疫组织化学评估242例浸润性肺癌和43例浸润前肺癌中磷酸化Akt的表达，并将我们的发现与临床结果相关联。PIK3CA在70%的鳞状细胞癌、38%的大细胞癌、19%的腺癌和67%的小细胞肺癌中扩增。经常观察到磷酸化Akt过表达，根据核或细胞质定位，在12%至17%的肺癌中过表达强烈。PIK3CA基因拷贝数和磷酸化Akt蛋白表达均无预后意义。在浸润前病变中，PIK3CA的扩增和磷酸化Akt的过表达与重度发育异常相关，且二者也相互关联。这些观察结果表明PI3激酶途径在肺癌中频繁且早期参与。
