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Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma
Article first published online: 11 NOV 2004
Copyright © 2004 Wiley-Liss, Inc.
International Journal of Cancer
Volume 114, Issue 2, pages 166–173, 20 March 2005
How to Cite
Kubo, N., Yashiro, M., Ohira, M., Hori, T., Fujiwara, I. and Hirakawa, K. (2005), Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma. Int. J. Cancer, 114: 166–173. doi: 10.1002/ijc.20725
- Issue published online: 18 JAN 2005
- Article first published online: 11 NOV 2004
- Manuscript Accepted: 3 SEP 2004
- Manuscript Received: 17 MAY 2004
- Osaka City University Medical Research Foundation
- microsatellite instability;
- esophageal squamous cell carcinoma
Patients with esophageal squamous cell carcinoma (ESCC) frequently develop other primary cancers, such as gastric cancer and head and neck cancer. Details of carcinogenesis in patients with multiple primaries that include esophageal carcinoma with other primary carcinoma (ECOPC) remain uncertain. We examined microsatellite instability (MSI) status, frameshift mutation in target genes of MSI, mismatch repair protein expression and hypermethylation of the hMLH1 promoter region in ECOPC patients to better understand the underlying carcinogenic processes. High frequency MSI (MSI-H) was found in 15 (44.1%) of 34 patients with ECOPC, but in only 6 (14.3%) of 42 patients with esophageal cancer alone (p < 0.01). Frameshift mutations in TGFβRII, BAX, MSH3 and MSH6 genes respectively were present in 4, 1, 2 and 2 of 34 ECOPC patients. Immunohistochemical study showed that 12 (80.0%) of 15 MSI-H tumors showed loss of expression of either hMLH1 or hMSH2. In addition, 6 of 9 tumors (66.7%) that showed reduced hMLH1 expression also had hypermethylation of the hMLH1 promoter region. Our findings suggested that carcinogenesis in ECOPC was closely associated with the MSI pathway because of mismatch repair protein deficiency. © 2004 Wiley-Liss, Inc.