p53 mutations and overexpression affect prognosis of ovarian endometrioid cancer but not clear cell cancer.
OBJECTIVE
Although ovarian clear cell adenocarcinoma (OCCA) and ovarian endometrioid adenocarcinoma (EC) are considered to be closely related to endometriosis, the mechanisms of carcinogenesis of these two malignancies and malignant transformation of endometriosis are unclear. In this study, we examined the biology of OCCA and EC by performing large-scale analysis of K-ras activation and p53 mutation and overexpression in these malignancies. The results were subsequently analyzed for correlation with the clinicopathologic data.


METHODS
In the present study of OCCA and EC, we obtained clinicopathological data and analyzed frequency of mutations and overexpression of K-ras and p53. DNA was extracted from formalin-fixed, paraffin-embedded tissue, and target sequences were amplified in vitro by polymerase chain reaction. The DNA was analyzed for K-ras and p53 mutations by testing for single-strand conformation polymorphisms and by direct sequencing. Immunohistochemical staining was performed using p53 monoclonal antibody. Univariate analysis was performed using the Kaplan-Meier algorithm, and differences in survival were analyzed using the log rank test. The prognostic significance of the studied variables for survival was assessed using multivariate analysis with Cox regression analysis.


RESULTS
K-ras mutation was detected in 16.2% (6/37) of OCCA patients and 3.7% (1/27) of EC patients. No evidence of p53 mutation was detected in OCCA patients, but p53 mutation was detected in 63.0% of EC patients; these findings are consistent with the results of p53 immunohistochemistry. No statistical significance was observed for K-ras mutation in OCCA or EC. In EC patients, the absence of endometriosis and p53 overexpression was associated with a poorer survival. In OCCA patients tubulocystic and papillary histotype as well as stage II correlated with a worse survival.


CONCLUSIONS
p53 mutation, which was found in 63% of EC tumors, is an independent prognostic factor for EC patients. However, no p53 mutation was found in OCCA tumors. K-ras mutations did not affect survival of OCCA or EC patients.
Okuda
Tsuyoshi
T
Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
Otsuka
Junko
J
Sekizawa
Akihiko
A
Saito
Hiroshi
H
Makino
Reiko
R
Kushima
Miki
M
Farina
Antonio
A
Kuwano
Yuzuru
Y
Okai
Takashi
T
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003062:Codon; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D003062:Codon; D016159:Tumor Suppressor Protein p53