Molecular Subtypes of Gastric Cancer Are Associated in Part with Tumor Histology
Olga Speck, Weihua Tang, Douglas R Morgan, Michael O Meyers, Ricardo L Dominguez, Enrique Martinez, Pei-Fen Kuan, Margaret L Gulley. University of North Carolina Hospitals, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, Chapel Hill, NC; UNC Hospitals, Chapel Hill, NC; Western Regional Hospital, Santa Rosa de Copan, Honduras; Hospital Evangelico, Siguatepeque, Honduras; UNC, Chapel Hill, NC
Background: Gastric adenocarcinoma is one of the most common fatal malignancies worldwide and is characterized by marked morphologic and clinical heterogeneity. Intestinal and diffuse gastric cancers distinguished by the Lauren classification have different epidemiologic characteristics. Several additional distinct histologic types show prognostic differences. Gastric cancers that are infected with Epstein-Barr virus (EBV) may have yet another distinct clinicopathologic profile. Finally, gastric adenocarcinomas frequently exhibit neuroendocrine differentiation. In this study, we examined histologic features of gastric adenocarcinoma in correlation with molecular subtypes as defined by RNA expression profiling.
Design: H&E stained sections of 103 gastric adenocarcinomas were scored for 1) chronic and 2) acute inflammation, 3) stromal desmoplasia, 4) histologic subtype, 5) Lauren classification, 6) T stage, and 7) location within the stomach. Each paraffin embedded tumor was profiled on the Nanostring nCounter system targeting 93 human and viral RNAs and then was classified into molecular subtype by hierarchical clustering. Fisher's Exact test was used to analyze associations between each histologic variable and molecular subtype.
Results: In unsupervised analysis, cancers were clustered into three molecular subtypes. Group 1 (n=14) was EBV infected as confirmed by Q-PCR for DNA viral load and by EBER in situ hybridization. These cancers lacked neuroendocrine appearance in concert with low levels of GAST (gastrin) and CHGA (chromogranin) RNA, while they had significantly higher levels of chronic inflammation (p=0.0117) and decreased stromal desmoplasia (p=0.003). The uninfected cancers were divided into two molecular subtypes distinguished in part by moderate or high GAST and CHGA levels. Other parameters such as Lauren classification, anatomic location, and T stage were not associated with molecular subtype in this study.
Conclusions: These data suggest that molecular classification of gastric cancer could complement histologic evaluation to advance our understanding of disease biology and identify molecular signatures that distinguish gastric cancer subtypes.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 92, Wednesday Afternoon