Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5‐FU based chemotherapy after R0 resection

TLDR

The study examined whether microsatellite instability (MSI) status could serve as a prognostic biomarker and guide selection of patients who benefit from 5‑FU adjuvant chemotherapy. MSI status was assessed in 1,990 gastric cancer patients who underwent curative gastrectomy between 2005 and 2008 using PCR amplification of fluorescently labeled mononucleotide and dinucleotide microsatellite markers. MSI‑high tumors comprised 8.5% of patients and were associated with older age, female sex, distal location, lower stage, intestinal type, and differentiated histology; disease‑free survival did not differ by MSI status across stages, but 5‑FU adjuvant chemotherapy improved DFS only in MSS/MSI‑low patients, indicating MSI status can guide 5‑FU use in stage II/III gastric cancer after R0 resection.

Abstract

This study investigated whether MSI status can be used as a prognostic biomarker and whether it is helpful for predicting which patients will benefit from 5-FU based adjuvant chemotherapy. Between 2005 and 2008, an MSI status examination was performed in 1,990 gastric cancer patients who had undergone curative gastrectomy for gastric adenocarcinoma. MSI was analyzed by PCR amplification with fluorescent dye-labeled primers of mononucleotide markers (BAT25 and BAT26) and dinucleotide markers (D5S346, D2S123 and D17S250) specific to the microsatellite loci. Patients with MSI-H tumors accounted for 8.5% (n = 170) of the total study population. They tended to be older and female and to have distal tumor location, lower tumor stage, intestinal type of Lauren classification and differentiated histological type. The disease-free survival curves showed no significant differences between MSS/MSI-L and MSI-H patients at each stage of I, II, III and IV. In gastric cancer patients with stage II and III, 5-FU-based adjuvant chemotherapy showed better disease-free survival in the MSS/MSI-L group, but showed no benefits in the MSI-H group. By multivariate analysis, patients with MSS/MSI-L tumors benefited from 5-FU-based adjuvant chemotherapy in terms of tumor disease-free survival. MSI status in gastric cancer is not itself a prognostic indicator. However, it appears to be a possible guidance for the use of 5-FU-based chemotherapy in stage II and III gastric cancers after R0 resection.