Chemosensitivity and survival in gastric cancer patients with microsatellite instability

Abstract

4573 Background: High microsatellite instability (MSI-H) occurs in about 10% of all gastric cancers and both the clinical and pathological features differ in tumors exhibiting either low microsatellite instability (MSI-L) or microsatellite stability (MSS). Conflicting data exist regarding the relevance of MSI for predicting the prognosis and benefits of 5-fluorouracil (5-FU) based chemotherapy in colon cancer patients. There have so far been no reports which describe the benefits of an MSI analysis of 5-FU treatment for gastric cancer. We therefore investigated the usefulness of MSI as a predictor of distinct clinical attributes influencing the overall survival (OS) based on the use of adjuvant chemotherapy with 5-FU and its analogue in gastric cancer. Methods: We collected data and tumor specimens from 240 consecutive gastric cancer patients from 1993 to 2002. Five Microsatellite loci were analyzed using a high intensity micorosatellite analysis we reported previously. The Cox proportional hazard model was used to compare the clinical data and survival as well as any associations for MSI and the 5-FU treatment status of patients with MSI or MSS gastric cancers. In 147 cases, the MTT assay was conducted to investigate the chemosensitivity of 5-FU. Results: We identified 25 MSI-H (10.7%), 22 MSI-L (9.4%) and 193 MSS (79.9%) tumours. Gastric cancer with MSI-L/H tended to have an increased likelihood of metastasizing to the regional lymph nodes and thereby show lymph vessel involvement (p<0.05). In an analysis that did not take into account the use of chemotherapy, univariate and multivariate analyses failed to show any difference between the MSI-H/L and MSS groups with respect to the overall survival. Furthermore, the survival after the administration of 5-FU did not correlate with the MSI status. When the chemotherapeutic sensibilities of these patients were studied in an MTT assay, MSI was not associated with the 5-FU sensitivity. Conclusions: The results of this study indicate that the MSI status has no clear influence on the overall survival and response to 5-FU in gastric cancer. However, MSI was observed to play an important role in either lymph node metastasis or lymph vessel involvement, in the same manner as that observed for colon cancer. No significant financial relationships to disclose.