Synchronous multiple primary gastrointestinal cancer exhibits frequent microsatellite instability

• Published in: International journal of cancer Vol. 86; no. 5; pp. 678 - 683
• Main Authors: Ohtani, Hiroshi, Yashiro, Masakazu, Onoda, Naoyoshi, Nishioka, Nobuaki, Kato, Yasuyuki, Yamamoto, Shinji, Fukushima, Shoji, Hirakawa‐Ys Chung, Kosei
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.06.2000
• Subjects: Aged; Aged, 80 and over; bcl-2-Associated X Protein; DNA-Binding Proteins - genetics; Female; Frameshift Mutation; Gastrointestinal Neoplasms - genetics; Humans; Loss of Heterozygosity; Male; Microsatellite Repeats; Middle Aged; Multidrug Resistance-Associated Proteins; MutS Homolog 3 Protein; Neoplasms, Multiple Primary - genetics; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Receptor, IGF Type 2 - genetics; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta - genetics
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(20000601)86:5<678::AID-IJC12>3.0.CO;2-O

Colorectal (CRC) and gastric cancers (GC), the most common gastrointestinal malignancies, have been known to develop occasionally in a same patient. Previous studies have focused on the etiology of patients with multiple primary gastric and colorectal cancer (MPGCC); however, the carcinogenic process of MPGCC remains unclear. In this study, we have examined the genetic alterations in MPGCC in order to clarify the carcinogenic pathway. Twenty patients with sporadic MPGCC were examined for microsatellite instability (MSI) and frameshift mutations of target genes such as TGFβRII, BAX and IGFIIR. In 10 (50%) of 20 patients with MPGCC, MSI was present at least at 1 lesion of GC or CRC. Four (50%) of 8 cases with synchronous MPGCC displayed MSI in both GC and CRC, while only 1 (8%) of 12 cases of metachronous MPGCC exhibited MSI in both organs. Carcinogenic process of MPGCC was fairly associated with the MSI pathway, particularly in cases of synchronous MPGCC. MSI was found in 5 (25%) of 20 GCs and in 10 (50%) of 20 CRCs. MSI was involved more closely in CRC than in GC among MPGCC. Although most frameshift mutations at target genes were found in the MSI‐positive MPGCC, infrequent mutations were observed in the genes. Frameshift mutation was found in only 1 of 5 cases of MSI‐positive GC at TGFβRII. Only 2 of 10 cases of CRC with MSI showed mutation at TGFβRII, and 1 case also showed mutation at BAX and IGFIIR. Our findings suggest that TGFβRII, BAX and IGFIIR are not the main target genes for carcinogenesis in MSI‐positive MPGCC. Int. J. Cancer 86:678–683, 2000. © 2000 Wiley‐Liss, Inc.