Utility of molecular genetic signatures in the delineation of gastric neoplasia.

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.

• Authors: Mark Kidd, Irvin M Modlin, Shrikant M Mane, Robert L Camp, Geeta N Eick, Igor Latich, Michelle N Zikusoka
• Journal: Cancer (Cancer) Vol. 106 Issue 7 Pg. 1480-8 (Apr 01 2006) ISSN: 0008-543X [Print] United States
• PMID: 16502410 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2006 American Cancer Society.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens, Neoplasm
• Chromogranin A
• Chromogranins
• Genetic Markers
• MAGED2 protein, human
• MTA1 protein, human
• Repressor Proteins
• Trans-Activators
• Histone Deacetylases

Topics

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