ANALYSIS AND CLINICAL IMPLICATIONS OF K-RAS GENE-MUTATIONS AND INFECTION WITH HUMAN PAPILLOMAVIRUS TYPE-16 AND TYPE-18 IN PRIMARY ADENOCARCINOMA OF THE UTERINE CERVIX
P. Tenti et al., ANALYSIS AND CLINICAL IMPLICATIONS OF K-RAS GENE-MUTATIONS AND INFECTION WITH HUMAN PAPILLOMAVIRUS TYPE-16 AND TYPE-18 IN PRIMARY ADENOCARCINOMA OF THE UTERINE CERVIX, International journal of cancer, 64(1), 1995, pp. 9-13
Experimental models indicate that activated ras genes and HPV oncogeni
c sequences may cooperate in inducing a completely transformed phenoty
pe in epithelial cells. We searched for K-ras gene mutations and HPV t
ype-16 and -18 sequences in 67 primary adenocarcinomas of the uterine
cervix by analyzing DNAs from formalin-fixed, paraffin-embedded tissue
samples. Target sequences were amplified by PCR and analyzed by denat
uring gradient gel electrophoresis (DGGE) and sequencing for the detec
tion of K-ras gene mutations and by Southern blotting for the detectio
n of HPV infection. We found 16 mutations in 15 cases; 14 were at codo
n 12 and 2 at codon 13;11 were base transitions and 5 were transversio
ns. Mutations were more frequent in mucin-secreting than in non-mucino
us tumors. HPV oncogenic sequences were detected in 58 cases with no s
ignificant difference between K-ras-mutated and wild-type tumors. HPV
oncogenic sequences were also more frequent in mucin-secreting than in
non-mucinous tumors. Both molecular events were present simultaneousl
y in 13 out of 58 cases, all of which had histologically grade-2 and g
rade-3 tumors. Clinicopathological parameters of the disease and the o
verall survival, however, were independent of K-ras mutations and of H
PV-16 and -18 infection, as shown by univariate and multivariate analy
sis. In contrast, stage of disease, lymph-node metastases, deep infilt
ration, clear-cell histology and low grade of differentiation were ris
k factors for tumor-related death. (C) 1995 Wiley-Liss, Inc.