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.

• Authors: Jin Man Kim, Dong Wook Kang, Liang Zhe Long, Song-Mei Huang, Min-Kyung Yeo, Eunhee S Yi, Kyung-Hee Kim
• Journal: Human pathology (Hum Pathol) Vol. 42 Issue 3 Pg. 315-23 (Mar 2011) ISSN: 1532-8392 [Electronic] United States
• PMID: 21190720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cyclins
• EGFR protein, human
• ErbB Receptors
• 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
• ErbB Receptors (genetics, metabolism)
• 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)
• Tissue Array Analysis