1. ¹Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA, USA
2. ²Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA
3. ³Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA

Correspondence: Dr SM Powell, Digestive Health Center of Excellence, University of Virginia Health System, PO Box 800708, Charlottesville, VA 22908-0708. USA. E-mail: powell@virginia.edu

Received 5 May 2005; Revised 25 July 2005; Accepted 25 July 2005; Published online 10 October 2005.

Abstract

CCAAT element binding protein beta (C/EBP) is an important regulator of cell growth, differentiation and in promoting tumor invasiveness. C/EBP is located on chromosome 20q, which is amplified in many solid tumors including gastric cancers (GC). We sought to characterize the status of C/EBP expression in GCs, which was recently found to repres TFF1 gene. Microarray analysis revealed overexpression of C/EBP in 25 of 27 (93%) GC when compared to 12 normal gastric tissue samples. RT–PCR analysis confirmed the overexpression of C/EBP transcripts in 54 of 59 (91%) GC. In total, 15 of 18 gastric tumors exhibited at least fivefold higher C/EBP transcript levels compared to their corresponding adjacent normal gastric tissue samples. Moreover, immunohistochemistry analysis demonstrated increased nuclear staining of C/EBP in 10 of 13 GC and at least fourfold overexpression of C/EBP in three primary GC compared to adjacent normal gastric tissue. Furthermore, a striking correlation of decreased TFF1 expression with increased C/EBP was observed in the gastric tumors studied. Microarray analysis demonstrated a loss of TFF1 expression in all 27 GC cases examined, of which 25 exhibited high C/EBP expression compared to normal gastric tissue. RT–PCR analysis revealed loss of TFF1 expression in 56 of 59 gastric tumors in which 54 of these tumors exhibited overexpression of C/EBP. Immunohistochemical analysis revealed overexpression of C/EBP in 10 of 13 gastric tumors that exhibited low expression of TFF1 at the protein level. Thus, overexpression of the transcription factor C/EBP in the majority of GCs is a novel finding.