Assessment of Microsatellite Instability in Familial Gastric Cancer

Background: Classically, gastric cancer (GC) appears as sporadic form, nonetheless recently a very high familial aggregation rates have been recently described in high incidence areas. Microsatellite instability (MSI) is recognized as an important molecular pathway in gastric tumor. The aim of this study was to assess the frequency of MSI in GC with familial aggregation. Methods: Five quasimonomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21 and NR-27) were analyzed in 250 GC patients and analyzed with respect to family history. Results: Seventy-five patients (30%) had at least one firstdegree family member affected by GC and MSI was identified in 63 patients (25.2%). MSI was significantly more frequent in patients with familial aggregation for GC (38.7% vs. 19.4%; P=0.001). Even stratifying according to Lauren histotype, a significant associationbetween MSI status and familial aggregation for GC was observed in intestinal as well as non–intestinal Lauren histotype. A similar frequency of MSI was observed in families with history of GC only or in families with members with colon cancer (P=0.96). Conversely, in families with history of lung cancer the frequency of MSI cases was significantly lower (5.6%) (P=0.007). Conclusions: MSI occurs in GC with familial aggregation, especially in families with members affected with gastric cancer as sole neoplasia or with colon cancer. The same in not verified in families with lung cancer. These data suggests that the first two types of families share common ethiological factors in contrast to GC families with involvement of lung cancer.