title: 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.affiliation: Department of Pathology, Daejeon Regional Cancer Center, Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Liang Zhe
authors.initials: LZ
authors.lastname: Long
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Yeo
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D016213:Cyclins / Q000378:metabolism*; D003952:Diagnostic Imaging; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D016213:Cyclins; C512478:EGFR protein, human; D066246:ErbB Receptors; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human; D019950:Mitogen-Activated Protein Kinase 1