A1 Refereed original research article in a scientific journal

Gastric cancer: immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics




AuthorsEva-Maria Birkman, Naziha Mansuri, Samu Kurki, Annika Ålgars, Minnamaija Lintunen, Raija Ristamäki, Jari Sundström, Olli Carpén

PublisherSpringer Berlin Heidelberg

Publication year2018

JournalVirchows Archiv

Volume472

Issue3

First page 369

Last page382

Number of pages14

ISSN0945-6317

DOIhttps://doi.org/10.1007/s00428-017-2240-x

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/27657960


Abstract

Gastric cancer is traditionally divided into intestinal and diffuse
histological subtypes, but recent molecular analyses have led to novel
classification proposals based on genomic alterations. While the
intestinal- and diffuse-type tumours are distinguishable from each other
at the molecular level, intestinal-type tumours have more diverse
molecular profile. The technology required for comprehensive molecular
analysis is expensive and not applicable for routine clinical
diagnostics. In this study, we have used immunohistochemistry and in
situ hybridisation in molecular classification of gastric
adenocarcinomas with an emphasis on the intestinal subtype. A tissue
microarray consisting of 244 gastric adenocarcinomas was constructed,
and the tumours were divided into four subgroups based on the presence
of Epstein-Barr virus, TP53 aberrations and microsatellite instability.
The intestinal- and diffuse-type tumours were separately examined. The
distribution of EGFR and HER2 gene amplifications was studied in the
intestinal-type tumours. Epstein-Barr virus positive intestinal-type
tumours were more common in male patients (p = 0.035) and most often
found in the gastric corpus (p = 0.011). The majority of the
intestinal-type tumours with TP53 aberrations were proximally located
(p = 0.010). All tumours with microsatellite instability showed
intestinal-type histology (p = 0.017) and were associated with increased
overall survival both in the univariate (p = 0.040) and multivariate
analysis (p = 0.015). In conclusion, this study shows that gastric
adenocarcinomas can be classified into biologically and clinically
different subgroups by using a simple method also applicable for
clinical diagnostics.


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