Clinicopathologic characteristics of microsatellite instability (MSI) tumors in resected gastric cancer patients.

Abstract

4040 Background: The DNA mismatch repair (MMR) pathway plays a prominent role in the correction of errors made during DNA replication and genetic recombination and in the repair of small deletions and loops in DNA. Defects in MMR can precipitate microsatellite instability (MSI). DNA MMR also plays a role in the toxicity and the efficacy of DNA-damaging agents including cisplatin. Several PARP inhibitors were developed and showed potentiating the effects of DNA damaging agents. We investigated the frequency of MSI tumors in gastric cancer patients for future clinical trial and explored whether these tumors are associated with specific clinicopathologic characteristics. Methods: Between Feb 2005 and Jan 2006, 732 consecutive gastric cancer patients who received curative resection with D2 dissection in Seoul National University Hospital were recruited for MSI analysis. MSI status was determined using all five of the NCI recommended panel of markers (BAT26, BAT25, D2S123, D5S346 and D17S250). Results: MSI-H (2 or more markers of instability) and MSI-L (only 1 marker of instability) phenotype was observed in 72 (9.8%) and 48 patients (6.6%), respectively. MSI-H was associated with older age (p < 0.0001), well or moderate differentiation (p < 0.0001), intestinal type (p < 0.0001), antral location (p < 0.0001) and presence of lymphatic invasion (p < 0.0001). After 44.2 months of median follow up, 101 patients (13.8%) experienced disease recurrence and MSI-H was associated with longer disease-free survival (DFS), although statistical significance was not reached yet (p = 0.148). Conclusions: Gastric cancer with MSI-H phenotype had specific clinicopathologic features and showed a tendency of longer DFS compared with MSI-L/MSS phenotype. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AZ-KCSG Fellowship