Prognostic and Putative Predictive Biomarkers of Gastric... : Diagnostic Molecular Pathology (original) (raw)

Original Articles

Prognostic and Putative Predictive Biomarkers of Gastric Cancer for Personalized Medicine

Warneke, Viktoria S. MD*; Behrens, Hans-Michael MSc*,†; Haag, Jochen PhD*; Balschun, Katharina MD*; Böger, Christine MD*; Becker, Thomas MD, PhD‡; Ebert, Matthias P.A. MD, PhD§; Lordick, Florian MD, PhD∥; Röcken, Christoph MD, PhD*

Departments of *Pathology

‡General Surgery and Thoracic Surgery, Christian-Albrechts-University, Kiel

†Department of Pathology, Charité University Hospital, Berlin

§Department of Medicine II, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim

∥University Cancer Center Leipzig (UCCL), University of Leipzig, Leipzig, Germany

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.molecularpathology.com.

V.S.W. and H.-M.B. share first authorship.

C.R. is supported by grants of the Deutsche Forschungsgemeinschaft (Grant No. Ro 1173/11 and Ro 1173/12).

The authors declare no conflict of interest.

Reprints: Christoph Röcken, MD, PhD, Department of Pathology, Christian-Albrechts University, Arnold-Heller-Str. 3, Haus 14, D-24105 Kiel, Germany (e-mail: [email protected]).

Abstract

We investigated various phenotypic and genotypic biomarkers of gastric cancer (GC) testing the following hypotheses: are these biomarkers suitable for the identification of GC subtypes, are they of prognostic significance, and should any of these biomarkers be considered to tailor patient treatment in the future. The study cohort consisted of 482 patients. pTNM-stage was based on surgical pathologic examination. The Laurén and mucin phenotype was assessed. Helicobacter pylori and Epstein-Barr virus infections were documented. The following biomarkers were determined: BRAF, KRAS, NRAS, and PIK3CA genotype, microsatellite instability, mucin 1, mucin 2, mucin 5, and mucin 6, CD10, E-cadherin, β-catenin, and lysozyme. The histologic phenotype correlated with 10/13 (77%) clinicopathologic patient characteristics and 6/13 (46%) immunohistochemical/molecular biological biomarkers. Inversely, immunohistochemical biomarkers (mucin phenotype, E-cadherin, β-catenin, and lysozyme) were unsuitable for subclassification of GC. It showed too much overlap between the different subtypes. Among the genotypes, only microsatellite instability correlated with tumor type being more prevalent in intestinal and unclassified GCs. Patient survival correlated significantly with 8 (62%) clinicopathologic and 5 (36%) immunohistochemical/molecular biomarkers. Interestingly, in proximal GCs, KRAS mutation was associated with worse prognosis, as was persistent H. pylori infection in unclassified GCs. Mucin 2 (all patients, proximal GCs) and PIK3CA (exon 20; intestinal type GC) prognosticated independently patient survival. The biomarkers examined herein are unsuitable to aid histologic classification of GC. However, several of them show a correlation with either phenotype and/or prognosis and may be considered to tailor patient treatment in the future, such as KRAS, PIK3CA, MSI, and H. pylori status.