The TCGA proposed molecular division of GC into four subgroups, based on genomic clustering combined to the molecular data: Epstein-Barr

Transl Gastroenterol Hepatol 2016;1:11 tgh.amegroups. com Gastric cancer (GC) is a very heterogeneous disease. Despite the decreasing incidence with time, it represents the second most common cause of cancer-related death after lung cancer; however, it is well known that incidence rates are very different throughout the world, with some geographic areas showing much higher rates than other regions (1,2). Subtypes of GC present different and sometimes opposite epidemiological trends, with reference to proximal vs. distal tumor locations, or intestinal vs. diffuse Lauren histological types (3). Along with wide variat ions in epidemiological characteristics, survival probabilities of GC patients are also different between Countries or risk areas in the same country (4). In a report from the EUROCARE Working Group, the improvement in 5-year relative survival of GC during a decade was negligible (4.1% in males and 1.4% in females) (5). Notably, GC exhibited the largest variability in survival rates among European countries, much more than other neoplasms, as breast or colorectal cancer. A recent study from our group also demonstrated strong differences in long-term outcome in GC patients coming from high or low risk areas of Italy, and treated at the same center with a similar surgical approach (6). The exact reasons of such prognostic variability are still unknown, because differences in tumor (location, histotype) and individual characteristics (age, gender) are not able to completely explain these disparities (7). In general, it seems that a correlation exists between incidence and survival rates. Indeed, the highest is the incidence, the highest seems to be the survival probability (7,8). We could speculate, as possible explanation of this phenomenon, that different biological form of GC may be linked to its epidemiology; more aggressive forms may have a uniform incidence throughout the world, whereas less aggressive forms may be more prevalent in high-risk areas. This could lead to better survival probability when the survivals of overall GC cases are analyzed in such areas (8). Microsatellite instability (MSI) has been reported, in several studies, as an important favourable prognostic factor for GC; we recently confirmed its prognostic value in a large series (9). Furthermore, in our experience we observed a different proportion of MSI cases in patients coming from high-risk or low-risk areas of Italy, being MSI more common in regions with higher GC incidence (manuscript to be submitted). An alarming feature linked to this aspect is that the decreasing incidence of GC, above all in high-risk areas, may be due to the decreasing number of less aggressive forms. As a result, in the future we could observed less GC case, but with more aggressive tumor biology (3). Two recent important studies which analyzed molecular biological characteristics of GC, the The Cancer Genome Atlas (TCGA) in America and Asian Cancer Research Group (ACGR) in Asian countries, may be helpful to provide possible explanations for these clinical heterogeneities (10,11). The TCGA proposed molecular division of GC into four subgroups, based on genomic clustering combined to the molecular data: Epstein-Barr virus (EBV)-positive, microsatellite unstable tumors (MSI), genomically stable (GS) and chromosomally instable (CIN) GC. The ACRG proposed a division into MSI, and three microsatellite stable subtypes: epithelial—to mesenchymal transition (MSS/EMT), p53 positive (MSS/TP53+), and p53 negative Commentary