It has been well established that specific alterations in members of the ras gene family, Hras, Kras and Nras, can convert them into active oncogenes. These alterations are either point mutations occuring in either codon 12, 13 or 61, or
alternatively, a 5to 50fold amplification of the wildtype gene. Activated ras oncogenes have been found in a significant proportion of all tumors, but the incidence varies considerably with the tumor type : it is frequent (20∼40 %) in
colorectal
cancer and acute myeloid leukemia, but absent or present rarely in breast and stomach cancer. But the role of cKras point mutation in the development of cancers in the female genital tract has not been extensively studied. Polymerase chain
reaction
followed by gel electrophoresis was performed respectively using wildtype normal and specific point mutation primers(GGT→GAT, GGT→GAT, GGT→TGT and GGT→GGT) to detect point mutation of codon 12 c-k-ras oncogene. The c-K-ras oncogene point
mutation
was confirmed by Southern blot hybridization using synthetic oligonucleotide probes 3'end labelled with digoxigenindUTP. With this method, the frequency of point mutations on codon 12 cKras oncogene was examined the tissues in 37 cases of
ovarian cancer, 7 cases of endometrial cancer, 36 cases of the gestational trophoblastic tumor, 60 cases of cervical cancer.
The relationship between the presence of a cKras point mutation and clinicopathological characteristics of the female genital tract cancers were also analysed.
@ES The results were as follows;
@EN 1. The incidence of four point mutations on codon 12 of Kras oncogene in 37 ovarian cancers was 45.9% (17/37) and distribution were 43.2% (16/37), 2.7% (1/37) and 0% (0/37) in GGT→GAT, GGT→AGT, GGT→TGT, and GGT→GTT, respectively.
According to histological type, in ovarian cancers, The point mutation of Kras oncogene waspositive in 45 % (10/22) of serous cystadenocarcinomas. The incidence of four point mutations on codon 12 among 37 patients with ovarian cancer according
to
histological type was 45.5 % (10/22) with serous cystadenocarcinoma, 57.1% (4/7) of mucinous cystadenocarcinoma. Comparing the positive rate of point mutations of Kras oncogen among 37 patients with ovarian cancer with the clinical stage, point
mutation was detected in 28.5% (2/7) of patients with stage I, 40.0% (2/5) with stage Ⅱ, and 52.0% (13/25) with stage Ⅲ/Ⅳ. There was no statistically significant increasement of point mutations with the advance of the clinical stage of ovarian
cancer. Comparing the positive rate of point mutations of Kras oncogen among 37 patients with ovarian cancer according to the histologic grade point mutation was detected in 50.0 % (2/4) 0f patients with grade I, 451.7 % (5/12) with grade II
and
47.6
% (10/21) with grade III.
2. The incidence of point mutations of Kras oncogen among 33 patients with ovarian cancer who were performed pelvic lymph node dissection was 57.1 % (12/21) of the patients with pelvic lymph node metastases and 16.7% (2/12) of the patients
without
pelvic lymph node metastases. There was statistically significant difference between the positive rate of cKras point mutations and the pelvic lymph nodal status(P<0.05).
3. In 7 cases of endometrial cancer, positive rate of Kras point was 42.8 % (3/7). Point mutations were also detected in 2 cases from 4 choriocarcinomas, but, the point mutation was only detected in 1 case from 60 cervical carcinomas.
From these results, we may suggest that the point mutation on codon 12 cKras oncogene are considered to be one of the important genetic change in the tumor formation and progression of ovarian of cKras oncogene seems to be the one stop in
the
multistep process of tumor formation in ovarian cancer. Furthermore, the point mutation of c－k－ras gene could occur more frequently in the patients of ovarian cancer with pelvic lymph node metastases than in those without pelvic metastases,
suggesting
the orle in tumor progression. And we concluded that point mutation on codon 12 is comparable frequent in uterine endometrial carcinomas and have significance as an event that contributes to progrssion of endometrial cancers and choriocarcinoma,
but
cervical carcinoma do not appear to have cKras point mutation in general. More studies will be necessary, but the detection of ckras point mutation as the possibility of biological tumor marker to predict clinical outcome may be utilized
in
female malignancies.
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