Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

Anya N A Milne, Ralph Carvalho, Folkert M. Morsink, Alex R. Musler, Wendy W J De Leng, Ari Ristimäki, G. Johan A Offerhaus

Research output: Contribution to journalArticlepeer-review

Abstract

Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (≤45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in gastric adenocarcinomas compared to non-neoplastic mucosa, and in light of studies showing reduced risk of gastric cancer in nonsteroidal anti-inflammatory drug users, we have chosen to investigate the expression of COX-2 and related molecules in 113 early-onset gastric cancers and compare it with 91 conventional gastric cancers, using tissue microarrays. These markers include molecules known to be important in conventional gastric carcinogenesis, such as E-Cadherin, p53, COX-2, Trefoil Factor-1 (TFF1), β-catenin, p16 and c-myc; as well as molecules not yet described as being important in gastric cancer, such as the transcription factor c-jun, the COX-2 mRNA stabilizer HuR, and C/EBP-β, a transcription factor for COX-2. All markers showed a statistically significant difference between early-onset gastric cancers and conventional gastric cancers, using a χ2 test. In particular, early-onset gastric cancers displayed a COX-2 Low, TFF1-expressing phenotype, whereas COX-2 overexpression and loss of TFF1 was found in conventional cancers, and this difference between early-onset gastric cancers and conventional cancers remained statistically significant when adjusted for location and histology (P

Original languageEnglish (US)
Pages (from-to)564-572
Number of pages9
JournalModern Pathology
Volume19
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Keywords

  • COX-2
  • Early-onset gastric cancer
  • TFF1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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