Identification of a Subset of Human Non–Small Cell Lung Cancer Patients with High PI3Kβ and Low PTEN Expression, More Prevalent in Squamous Cell Carcinoma
| Autor: | David P. Blowers, Edward S. Kim, Carmen Behrens, Ignacio I. Wistuba, Chris Womack, Xinying Su, Neil Gray, Shuqiong Fan, Sabina Cosulich, Marie Cumberbatch, Sonia Eckersley, Xin Wang, Garry Beran, Simon Dearden, Ximing Tang, Rebecca Ellston, Paul D. Smith |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Lung Neoplasms Adenocarcinoma Article Phosphatidylinositol 3-Kinases Carcinoma Non-Small-Cell Lung medicine Carcinoma Humans PTEN Lung cancer In Situ Hybridization Fluorescence PI3K/AKT/mTOR pathway Tissue microarray biology PTEN Phosphohydrolase Cancer medicine.disease Immunohistochemistry Oncology Tissue Array Analysis Carcinoma Squamous Cell Cancer research biology.protein |
| Zdroj: | Clinical Cancer Research. 20:595-603 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-13-1638 |
| Popis: | Purpose: The phosphoinositide 3-kinase (PI3K) pathway is a major oncogenic signaling pathway and an attractive target for therapeutic intervention. Signaling through the PI3K pathway is moderated by the tumor suppressor PTEN, which is deficient or mutated in many human cancers. Molecular characterization of the PI3K signaling network has not been well defined in lung cancer; in particular, the role of PI3Kβ and its relation to PTEN in non–small cell lung cancer NSCLC remain unclear. Experimental Design: Antibodies directed against PI3Kβ and PTEN were validated and used to examine, by immunohistochemistry, expression in 240 NSCLC resection tissues [tissue microarray (TMA) set 1]. Preliminary observations were extended to an independent set of tissues (TMA set 2) comprising 820 NSCLC patient samples analyzed in a separate laboratory applying the same validated antibodies and staining protocols. The staining intensities for PI3Kβ and PTEN were explored and colocalization of these markers in individual tumor cores were correlated. Results: PI3Kβ expression was elevated significantly in squamous cell carcinomas (SCC) compared with adenocarcinomas. In contrast, PTEN loss was greater in SCC than in adenocarcinoma. Detailed correlative analyses of individual patient samples revealed a significantly greater proportion of SCC in TMA set 1 with higher PI3Kβ and lower PTEN expression when compared with adenocarcinoma. These findings were reinforced following independent analyses of TMA set 2. Conclusions: We identify for the first time a subset of NSCLC more prevalent in SCC, with elevated expression of PI3Kβ accompanied by a reduction/loss of PTEN, for whom selective PI3Kβ inhibitors may be predicted to achieve greater clinical benefit. Clin Cancer Res; 20(3); 595–603. ©2013 AACR. |
| Databáze: | OpenAIRE |
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