K- ras gene point mutations in human endometrial carcinomas: correlation with clinicopathological features and patients' outcome

Abstract

In order to evaluate the role of K-ras gene point mutations in the progression of endometrial carcinoma, we applied the polymerase chain reaction/restriction-fragment-length polymorphism technique to 57 tumours surgically removed from women of Polish origin. We assessed the relationship between K-ras gene activation and clinicopathological features as well as patients' outcome. Mutational activation in codon 12 of the K-ras gene was detected in 8 out of 57 (14%) endometrial carcinomas, while in codon 13 of the K-ras gene no point mutations were noted. A correlation between the histological type of the tumour and codon 12 K-ras gene mutation was noted (P < 0.05; Fisher exact test). K-ras gene mutation was not related to the patients' age, surgical stage, histological grade or to the depth of myometrial invasion. A trend towards a poorer prognosis was noted during the follow-up of patients whose tumours had shown K-ras codon 12 point mutations, but the difference was not significant (P = 0.06; log-rank test). Our data indicate that point mutations in codon 12 of the K-ras gene are a rare event in human endometrial carcinomas. The lack of correlation between K-ras point mutations and clinicopathological features (except histological type) supports the hypothesis of a random activation of the K-ras gene in human neoplastic endometrium.

Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis

“…The prognostic significance of KRAS mutation in this cancer is controversial. Most studies report no association with clinical outcome, [53][54][55][56] whereas others implicate KRAS activation as an unfavorable prognostic factor 57 or, conversely, as associated with improved prognosis. 18 These inconsistencies may depend on inclusion of cases from pathologically different groups.…”

“…In two separate European studies, the mutations were detected in aggressive histologic types (type 2 tumors) of endometrial carcinoma. 54,55 Thus, the role of KRAS in the two pathogenetic types of tumors needs to be further clarified. In this study, three tumors with KRAS mutation also showed a concomitant PTEN mutation, a finding in contrast with one previous study in which these mutations were found to be mutually exclusive.…”

K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene

“…K-ras mutations are considered to correlate with the phenotypic progression from atypical hyperplasia to endometrial cancer. A mutation in codon 12 of the K-ras gene has been identified in a range from 4.5 to 23% of atypical endometrial hyperplasia cases (Lagarda et al, 2001;Sun et al, 2002) and in from 11 to 26% of endometrioid carcinomas of the endometrium (Semczuk et al, 1998;Lax et al, 2000). The codons 12 and 14 of the K-ras gene are reported to be hotspots for carcinogen-DNA adduct formation in human bronchial epithelial cells (Feng et al, 2002).…”

The search continues: Looking for predictive biomarkers for response mTOR inhibition in endometrial cancer.

“…K-Ras mutations are also seen in 6-16% of endometrial atypical hyperplasia and thus, are considered one of the earliest molecular events in endometrial cancer. [10][11][12] Preliminary analysis in advanced solid tumors indicates that mutations in KRAS may convey resistance to PI3K-directed therapy, especially among endometrial cancer patients. 13 .…”