Frequent occurrence of c-Ki-ras gene mutations in well differentiated endometrial adenocarcinoma showing infiltrative local growth with fibrosing stromal response.
The frequency of c-Ki-ras mutation was examined by polymerase chain reaction (single-strand conformation polymorphism and direct sequencing analysis) and its association with histological parameters was analyzed in 110 endometrial adenocarcinoma hysterectomy specimens. The c-Ki-ras mutation was detected in 24 cases (22%). It occurred irrespective of tumor size, stage or histological grade, and was more frequent in tumors associated with endometrial hyperplasia (11 of 20, 55%) than in those without (10 of 73, 14%). In addition, the frequency of the mutation was significantly higher in tumors showing an infiltrative growth pattern accompanied by a stromal response consisting of edematous fibrous tissue (19 of 58, 33%), than in those which revealed an expansive growth pattern without such a stromal reaction (five of 52, 10%). Even among tumors showing the infiltrative growth pattern, the frequency of c-Ki-ras mutation was especially high (48%) in grade I cases in comparison with grade II or III cases (20% and 19%). Mutational activation of the c-Ki-ras gene may act at two points in the developmental pathway of endometrial adenocarcinoma by enhancing evolution of hyperplasia to adenocarcinoma, and by producing an infiltrative growth with a fibrosing stromal response.
Tsuda
H
H
Pathology Division, National Cancer Center Research Institute and Hospital, Tokyo, Japan.
Jiko
K
K
Yajima
M
M
Yamada
T
T
Tanemura
K
K
Tsunematsu
R
R
Ohmi
K
K
Sonoda
T
T
Hirohashi
S
S
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001483:Base Sequence; D004714:Endometrial Hyperplasia / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D017354:Point Mutation; D012189:Retrospective Studies; D015996:Survival Rate