PROGNOSTIC-SIGNIFICANCE OF RAS P21 ALTERATIONS IN HUMAN OVARIAN-CANCER/

Ras/p21 oncoprotein expression and K-ras mutations were analysed by We stern blot and/or K-ras oligonucleotide hybridization in 78 primary ov arian cancers, 20 omental metastases, two low malignant potential tumo urs (LMP), nine benign ovarian tumours and 10 normal ovaries. A cut-of f value of an integral of absorbance (i.a.) of 2.20, obtained by recei ver 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 carcinoma s (median 2.54 i.a. vs median 2.1 i.a.; P = 0.0089). p21 overexpressio n did not correlate with any of the clinicopathological parameters exa mined. Follow-up data were available for 63 patients. A significant re lationship was shown between p21 positivity and a shorter overall surv ival (OS) (P < 0.03) and progression-free survival (PFS) (P < 0.03). I n multivariate analysis only the presence of ascites, p21 levels and e pidermal growth factor receptor status retained an independent prognos tic role. K-ras gene mutations were frequently detected in benign and low malignant potential tumours (71.4%), which were mostly mucinous (P = 0.0152).