Analysis of microsatellite instability and loss of heterozygosity in uterine endometrial adenocarcinoma.
Microsatellite instability (MSI) and loss of heterozygosity (LOH) were examined in 60 cases of uterine endometrial adenocarcinoma, using 13 microsatellite markers. In non-Smad-related regions, MSI and LOH were noted in 13 of 60 (21.7%) and in 20 of 60 (33.3%) cases, respectively. Genetic alternation of TGF-beta RII was noted in 1 of 60 cases (1.7%). The frequency of MSI and LOH was highest in Stages III and IV, respectively. Cases with G2 carcinoma showed the highest frequency, but LOH frequency did not differ among G1, G2, and G3 carcinoma cases. In Smad-related microsatellite regions, MSI and LOH were noted in 10 of 60 (16.7%) and in 12 of 60 (20.0%) cases, respectively. The frequency of MSI and LOH was highest in Stages III and IV, respectively. LOH was seen only in the Smad2 gene but not in the Smad4 gene. Our results suggest that the alterations in MSI and LOH were associated with middle and late stages of carcinogenesis of endometrial carcinoma. Both MSI and LOH tended to show an association with moderate to severe atypia of carcinoma. Our results also suggest that genetic alteration of the Smad2 gene is more responsible for endometrial carcinogenesis than that of the Smad4 gene. However, the TGF-beta type II receptor gene was considered a minor target of genetic instability in endometrial carcinogenesis.
Toda
T
T
Department of Clinical Laboratory Medicine, University of the Ryukyus Hospital, School of Medicine, Nishihara-Cho, Aza Uehara 207, 903-0125, Okinawa, Japan.
Oku
H
H
Khaskhely
N M
NM
Moromizato
H
H
Ono
I
I
Murata
T
T
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators