Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer

Abstract

<p><b>Introduction </b>Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications. <br></p><p><b>Methods </b>We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH. <br></p><p><b>Results </b>In the univariate survival analysis for disease-specific survival, the Epstein-Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19-5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA's classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15-2.60], p = 0.009 and HR 1.74 [95% CI 1.06-2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial-mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30-2.77], p < 0.001) when compared with aberrant p53. <br></p><p><b>Conclusions </b>Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.<br></p>