A Multiple Testing Approach for Histological and Molecular Markers for Early Gastric Cancer
G Carrasco, P Ibanez, JR Valbuena, F Mena, FR Aguayo, C Ferreccio, A Corvalan. P.Universidad Catolica de Chile, Santiago, Chile; Hospital Max Peralta, Cartago, Costa Rica
Background: Gastric cancer (GC) is second leading cause of cancer-related death worldwide. The high mortality rate of GC is related with depth of invasion (Early or Advanced GC). To integrate histological and molecular markers in EGC we perfom multiple testing approach.
Design: Ninety one cases of EGC (tumor and normal adjacent mucosa, NAT) and 148 endoscopic biopsies from healthy donors were built into seven TMA blocks containing duplicates 1-mm thickness cores. Five histological (chronic inflammation, PMN, atrophic gastritis, intestinal metaplasia, H. pylori) and seven molecular markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73 and p16INK4a) were evaluated. For multiple testing approach, Significance Analysis of Microarrays (SAM) was applied. SAM identifies variables with statistically significant changes by assimilating a set of variable-specific t tests. Each variable is assigned a score on the basis of its change in variable expression relative to the standard deviation of repeated measurements for that variable.
Results: Clinical characteristics of EGCs and controls were similar. Chronic inflammation, atrophy and intestinal metaplasia were more frequent in NAT than in controls (p<0.00001). H.pylori infection was more frequent in controls (p<0.001). Molecular makers in EGC (tumor vs. NAT) were similar except for p53 overexpression in tumors (p<0.001). In NAT vs controls only p73 was overexpressed (p<0.001). SAM was applied to multiple testing including histological or molecular markers. SAM shows that NAT was characterized chronic inflammation, atrophy and intestinal metaplasia (p=0.00039, p<0.00001, p<0.00001) and overexpression of p73 (p=0.0061).
Conclusions: In the statistics of multiple testing, several methods can be applied (the family-wise error rate, the Westfall and Young step-down correction method and the method of Benjamini and Hochberg). Here, we have shown that SAM, a novel method for multiple testing, can be applied to integrate histological and molecular markers. SAM led us to confirm chronic inflammation, atrophy and intestinal metaplasia and identified p73 as a novel marker for EGC. Supported by FONDECYT 1080563.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 103, Tuesday Afternoon