title: A protein and mRNA expression-based classification of gastric cancer.
abstract: The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.
authors.affiliation: Pathology Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Setia
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Agoston T
authors.initials: AT
authors.lastname: Agoston
authors.affiliation: Pathology Service, Massachusetts General Hospital, Boston, MA, USA.|Konkuk University School of Medicine, Seoul, South Korea.
authors.forename: Hye S
authors.initials: HS
authors.lastname: Han
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Mullen
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Dan G
authors.initials: DG
authors.lastname: Duda
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.affiliation: Pathology Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Pathology Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Pathology Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jochen K
authors.initials: JK
authors.lastname: Lennerz
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.affiliation: Pathology Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D016159:Tumor Suppressor Protein p53