Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis

• DOI: 10.1002/path.1378
• Publication Date: 2003-07-29T10:14:40Z
• Authors: Yuan Chen; Thomas Knösel; Glen Kristiansen; Agnieszka Pietas; Mitchell E Garber; Sachiko Matsuhashi; Iwata Ozaki; Iver Petersen
• Keywords: Adult; Aged, 80 and over; 0301 basic medicine; Lung Neoplasms; Gene Expression; Adenocarcinoma; Middle Aged; Blotting, Northern; Prognosis; 3. Good health; Neoplasm Proteins; Immunoenzyme Techniques; 03 medical and health sciences; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Humans; RNA, Messenger; RNA, Neoplasm; Apoptosis Regulatory Proteins; Aged; Follow-Up Studies; Oligonucleotide Array Sequence Analysis

AbstractThe programmed cell death 4 gene (PDCD4), a newly identified transformation suppressor, was analysed in lung tumour cell lines and primary lung carcinomas. Reduced PDCD4 mRNA expression was observed in two immortalized lung cell lines and 18 cancer cell lines by northern blot analysis. In the survey of primary lung tumours, PDCD4 cDNA was poorly represented in 47 lung tumours compared with normal lung tissue by cDNA microarray analysis and this poor representation was significantly associated with high‐grade (G3) adenocarcinomas (p = 0.012). Immunohistochemical analysis of 124 primary carcinomas comprising all subtypes demonstrated that PDCD4 protein expression was widely lost in tumour samples (83%) and was negatively related to poor prognosis (p = 0.013). The loss of PDCD4 expression correlated with higher grade and disease stage (p = 0.045 and 0.034, respectively), but not tumour size and nodal status. Similarly to the cDNA data, lack of PDCD4 expression was significantly linked to tumour grade in adenocarcinoma (n = 59, p = 0.048), while in squamous cell carcinoma (n = 58), no relationship between PDCD4 expression and clinicopathological parameters was established. These data suggest that the loss of PDCD4 expression is a prognostic factor in lung cancer and may correlate with tumour progression. Copyright © 2003 John Wiley & Sons, Ltd.