Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma

Abstract

BACKGROUND Since endoscopic treatment was first evaluated and established as a treatment for patients with early stage gastric carcinoma, metachronous disease recurrence at other sites in the stomach after endoscopic treatment has become a major problem. METHODS A retrospective case–control study was conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful endoscopic mucosal resection (EMR) therapy for early stage gastric carcinoma and on 14 patients without recurrence. Gastric mucosal tissues obtained during the initial EMR were dissected, and DNA samples from the tumor tissue and surrounding nonneoplastic mucosa were extracted separately. Microsatellite instability (MSI) was tested in five microsatellite markers (D2S137, D3S1067, TP53, TGFβRII, and BAX). The authors also looked for K‐ras codon 12 point mutations in the tumor tissues. In addition, immunohistochemical staining was done to test for the presence of proliferating cell nuclear antigen (PCNA), p53, hMSH2, and hMLH1 in the mucosal tissues. Finally, the correlation between the presence or absence of metachronous recurrence and the characteristics of the primary tumor (MSI, K‐ras, p53, etc.) were investigated. RESULTS Three of 10 patients with recurrent disease showed MSI in more than two microsatellite markers among 3–5 investigated site (MSI‐H), whereas none of the patients with nonrecurrent disease did so. There was no significant correlation between metachronous recurrence after EMR and immunohistochemical staining reactions, including those for PCNA, p53, hMSH2, and hMLH1. None of the patients showed K‐ras mutations. CONCLUSIONS Thirty percent of patients with recurrent disease showed MSI‐H, whereas none of the patients with nonrecurrent disease did so. Cancer 2001;91:339–45. © 2001 American Cancer Society.

Fetal-type Glycogen Phosphorylase (FGP)Expression in Intestinal Metaplasia as a High Risk Factor of the Development of Gastric Carcinoma

“…The important thing is to have a good predictor for metachronous recurrence after local treatment [41,48]. Our study demonstrated that FGP-positive IM was detected even in the stomachs with endoscopic atrophic gastritis without any malignant lesion, suggesting that FGP-positive IM was not a pathological entity which was associated with the change of a carcinogenic microenvironment in the gastric mucosa.…”

“…One of the major problems with the local treatment of gastric cancer is that of the metachronous carcinomas in other parts of the stomach being different from the initial site of the carcinoma. A recent molecular biological study has suggested that high microsatellite instability in gastric tumors had a relationship with synchronous and/or metachronous gastric cancer compared with single carcinoma, whereas there was no difference in proliferative ability, carcinogenic pathway through p53 or K-ras, and various mismatch repair genes, although the mechanism was unclear [48]. However, the application of molecular genetics in the screening and surveillance of the patients with gastric cancer is still in its infancy.…”

Genetic and Epigenetic Markers to Identify High Risk Patients for Multiple Early Gastric Cancers after Treatment with Endoscopic Mucosal Resection

“…There were some reports about MSI or hypermethylation of tumor-related genes in multiple gastric cancers [ 14 – 16 ]. Miyoshi et al [ 14 ] showed that the frequency of MSI was significantly higher in the patients with multiple gastric cancers, both synchronous and metachronous, than in those with a single gastric cancer.…”

“…Several reports have been published about methylation of various genes, including hMLH1 , O 6 -methylguanine DNA methylyransferase (MGMT) , E-cadherin and p16 , in chronic gastritis, intestinal metaplasia and adenomas to carcinomas of the stomach [ 9 – 13 ]. However, few reports have described about the correlation between the presence of MSI and DNA hypermethylation in multiple gastric cancers [ 14 – 16 ]. In order to find genetic and epigenetic markers to identify high risk patients for multiple early gastric cancers after treatment with endoscopic mucosal resection (EMR), we analyzed the MSI status and hypermethylation of multiple tumor-related genes in these patients comparing single gastric cancer with synchronous and metachronous multiple gastric cancers.…”

Long-term outcome and surveillance policy after endoscopic therapy for early gastric cancer

“…Other possible intervention includes nutritional supplementation [16] or medication such as Cox-2 inhibitor with antineoplastic properties [17]. Recently, such cancers have been found to harbor defects in the mismatch repair system, presenting high microsatellite instability (MSI-H) [18,19]. MSI-positive gastric cancers often show silencing of mismatch repair genes such as the hMLH1 gene by promoter hypermethylation.…”