Utility of molecular genetic signatures in the delineation of gastric neoplasia

Cancer. 2006 Apr 1;106(7):1480-8. doi: 10.1002/cncr.21758.

Abstract

Background: Current techniques to define gastric neoplasia are limited but molecular genetic signatures can categorize tumors and provide biological rationale for predicting clinical behavior. We identified three gene signatures: Chromogranin A (CgA), MAGE-D2 (adhesion), and MTA1 (metastasis) that define gastrointestinal (GI) carcinoids and hypothesize that their expression can delineate gastric neoplasia. This strategy provides a molecular basis to define neuroendocrine gastric carcinoids (GCs), neuronal stromal tumors (GISTs), or epithelial cell (gastric adenocarcinomas [GCAs])-derived tumors.

Methods: Total RNA was isolated from 38 GCs: Type I/II (n = 7), Type III/IV (n = 6), GISTs (n = 12), GCAs (n = 13), and normal mucosa (n = 12). Quantitative reverse transcriptase polymerase chain reaction (Q RT-PCR) gene expression was quantified against glyseraldehyde-3-phosphate dehydrogenase (GAPDH) and CgA and MTA1 protein expression levels were analyzed by immunohistochemical analyses of a gastric neoplasia microarray.

Results: CgA was elevated in Type I/II (10-fold; P < .01) and Type III/IV (100-fold, P < .005), decreased in GISTs (100-fold, P < .03), and unchanged in GCAs. MAGE-D2 was 5-10-fold elevated (P < .05) in Type III/IV, GISTs, and GCAs but not in Type I/II tumors. MTA1 (> 5-fold, P < .01) was elevated in GCs (Type III/IV>I/II, P < .05), in GISTs (> 4-fold, P < .05), and GCAs. CgA protein levels were elevated in GCs (P < .005) but not in GISTs and GCAs. MTA1 levels were elevated in all tumors (P < .02) compared with normal, and especially with tumor invasion (P < .05).

Conclusion: CgA discriminates GCs from other gastric neoplasms; overexpression of MAGE-D2 and MTA1 differentiate Type III/IV from Type I/II GCs. GISTs share similar expression patterns with Type III/IV GCs but have decreased CgA. MTA1 is a marker of tumor invasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma / classification
  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics*
  • Carcinoid Tumor / classification
  • Carcinoid Tumor / diagnosis
  • Carcinoid Tumor / genetics*
  • Chromogranin A
  • Chromogranins / biosynthesis
  • Chromogranins / genetics*
  • Diagnosis, Differential
  • Female
  • Gene Expression Profiling
  • Genetic Markers
  • Histone Deacetylases / biosynthesis
  • Histone Deacetylases / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / classification
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Neoplasm
  • Chromogranin A
  • Chromogranins
  • Genetic Markers
  • MAGED2 protein, human
  • Mta1 protein, human
  • Repressor Proteins
  • Histone Deacetylases