Prognostic significance of ras/p21 alterations in human ovarian cancer.
Ras/p21 oncoprotein expression and K-ras mutations were analysed by Western blot and/or K-ras oligonucleotide hybridization in 78 primary ovarian cancers, 20 omental metastases, two low malignant potential tumours (LMP), nine benign ovarian tumours and 10 normal ovaries. A cut-off value of an integral of absorbance (i.a.) of 2.20, obtained by receiver operating characteristic (ROC) curve, was shown to be the best cut-off for defining p21 positivity. p21 levels were higher in malignant tumours than in benign tumours (median 2.10 i.a. vs median 1.22 i.a.; P = 0.014) and in omental metastases than in primary ovarian carcinomas (median 2.54 i.a. vs median 2.1 i.a.; P = 0.0089). p21 overexpression did not correlate with any of the clinicopathological parameters examined. Follow-up data were available for 63 patients. A significant relationship was shown between p21 positivity and a shorter overall survival (OS) (P < 0.03) and progression-free survival (PFS) (P < 0.03). In multivariate analysis only the presence of ascites, p21 levels and epidermal growth factor receptor status retained an independent prognostic role. K-ras gene mutations were frequently detected in benign and low malignant potential tumours (71.4%), which were mostly mucinous (P = 0.0152).
Scambia
G
G
Department of Gynecology and Obstetrics, Catholic University, Rome, Italy.
Masciullo
V
V
Benedetti Panici
P
P
Marone
M
M
Ferrandina
G
G
Todaro
N
N
Bellacosa
A
A
Jain
S K
SK
Neri
G
G
Piffanelli
A
A
Mancuso
S
S
D000818:Animals; D015153:Blotting, Western; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras; D006801:Humans; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D017354:Point Mutation; D011379:Prognosis; D016019:Survival Analysis
D015689:Oncogene Protein p21(ras)