Journal
CANCER
Volume 106, Issue 7, Pages 1480-1488Publisher
WILEY
DOI: 10.1002/cncr.21758
Keywords
AQUA; carcinoid; gastric; invasive phenotype; malignancy; PCR; tissue microarray
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Funding
- NCI NIH HHS [R01-CA-097050] Funding Source: Medline
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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 (it = 12), GCAs (n = 13), and normal mucosa (n = 12). Quantitative reverse transcriptase polymerase chain reaction (QRT-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.
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