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Differential expression of Yes-associated protein is correlated with expression of cell cycle markers and pathologic TNM staging in non-small-cell lung carcinoma.

Abstract
Yes-associated protein, a downstream effector of the Hippo signaling pathway, has been linked to progression of non-small-cell lung carcinoma. The aim of this study was to investigate expression of Yes-associated protein in lung adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated protein expression with clinicopathologic parameters, expression of cell cycle-specific markers, and epidermal growth factor receptor gene amplification were also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear expression of Yes-associated protein was significantly correlated with expression of cyclin A and mitogen-activated protein kinase. Multivariate analysis, including age and sex, showed that cyclin A expression was independently correlated with nuclear expression of Yes-associated protein in adenocarcinomas. Furthermore, high nuclear expression of Yes-associated protein was also a significant predictor of epidermal growth factor receptor gene amplification for adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis revealed that high cytoplasmic expression of Yes-associated protein was correlated with the low pathologic TNM staging (stage I) and histologic grading. Multivariate analysis, including age and sex, showed that cytoplasmic expression of Yes-associated protein was an independent predictor of low pathologic TNM staging. These results indicate that nuclear overexpression of Yes-associated protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic expression of Yes-associated protein is an independent predictor of low pathologic TNM staging and histologic grading. The differential effects of Yes-associated protein expression patterns in adenocarcinomas and squamous cell carcinomas suggest that Yes-associated protein may play important roles in different pathways in distinct tumor subtypes. These observations may, therefore, lead to new perspectives on therapeutic targeting of these tumor types.
AuthorsJin Man Kim, Dong Wook Kang, Liang Zhe Long, Song-Mei Huang, Min-Kyung Yeo, Eunhee S Yi, Kyung-Hee Kim
JournalHuman pathology (Hum Pathol) Vol. 42 Issue 3 Pg. 315-23 (Mar 2011) ISSN: 1532-8392 [Electronic] United States
PMID21190720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Cyclins
  • EGFR protein, human
  • Receptor, Epidermal Growth Factor
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human
  • Mitogen-Activated Protein Kinase 1
Topics
  • Carcinoma, Non-Small-Cell Lung (diagnosis, genetics, metabolism)
  • Carcinoma, Squamous Cell (diagnosis, genetics, metabolism)
  • Cell Nucleus (metabolism, pathology)
  • Cyclins (metabolism)
  • Diagnostic Imaging
  • Female
  • Gene Amplification
  • Gene Dosage
  • Humans
  • In Situ Hybridization
  • Lung Neoplasms (diagnosis, genetics, metabolism)
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-yes (genetics, metabolism)
  • Receptor, Epidermal Growth Factor (genetics, metabolism)
  • Tissue Array Analysis

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