Microsatellite instability is often observed in esophageal carcinoma patients with allelic loss in the FHIT/FRA3B locus.
We have previously reported a significant correlation between the progression of colorectal carcinoma and the loss of Fhit and Msh2 expression. This observation led us to investigate the effect of an allelic loss of the FHIT gene on esophageal cancer when coupled with a deficient mismatch repair system. In this study, 8 of 42 patients with esophageal cancer had microsatellite instability (MSI), and 29 cases demonstrated allelic loss (loss of heterozygosity or homozygous deletion) at the FHIT/FRA3B locus. All 8 MSI-positive cases showed allelic loss, while 13 of 34 MSI-negative cases retained both alleles, and a significant correlation was found between the incidence of MSI and allelic loss (p < 0.05). On the other hand, only 1 of the 8 MSI-positive patients exhibited neither Msh2 nor Fhit protein expression in both normal and carcinoma epithelial tissues, but neither a relationship between Msh2 expression and Fhit expression nor with the incidence of MSI was noted. This result indicated that the disruption of the mismatch repair system of Msh2 does not mainly lead to allelic loss of the FHIT/FRA3B locus as well as MSI in esophageal cancer. We concluded that MSI is significantly related to the allelic loss in the FHIT/FRA3B region, but Msh2 might be unrelated to the progression or oncogenic process in esophageal cancer.
Mimori
Koshi
K
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu 874-0838, Japan.
Inoue
Hiroshi
H
Shiraishi
Takeshi
T
Matsuyama
Ayumi
A
Mafune
Ken-ichi
K
Tanaka
Yoichi
Y
Mori
Masaki
M
D017766:Acid Anhydride Hydrolases; D000368:Aged; D020137:Base Pair Mismatch; D002277:Carcinoma / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D004268:DNA-Binding Proteins; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C497172:MSH2 protein, human