Diagnostic approach using the expression profiling of the P53 tumor suppressor gene and its related proteins in ovarian epithelial tumors

Abstract

The initial aim of this study was to examine the expression profiles of P53 and its upstream genes, downstream genes, and cell cycle regulators to determine whether these markers are useful for making a differential diagnosis among the benign, borderline, and malignant ovarian epithelial tumors. Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each). Using the receiver operating curve (ROC), the most reliable cutoff value of the added-up staining scores of those markers was 4.5 with 79% sensitivity and 89% specificity for malignancy. Between benign and borderline tumors, the P21 and Bax expression levels were significantly higher in borderline tumors, whereas the Bcl-2 expression level was much higher in benign tumors (P < 0.01, each). Using the ROC, the cutoff value of the added-up staining scores used to discriminate between the two groups was 2.5 with 70% sensitivity and 74% specificity for borderline tumors. Thus, for the differential diagnosis between borderline and malignant tumors, the cutoff value 4.5 of the cumulative staining scores can be used. However, the cutoff value 2.5 for discrimination between benign and borderline tumors may not be useful because of its relatively low sensitivity and specificity. In addition, the P53, GADD45, Cyclin E, and MDM2 expression levels in malignant ovarian tumors might be useful for determining the histologic grade and type.

Distribution of p53 expression in tissue from 774 Danish ovarian tumour patients and its prognostic significance in ovarian carcinomas

“…The higher frequency of serous cystadenoma LMP with positive p53 expression in our study compared to other histological subtypes of LMP is in agreement with earlier studies (29,32,33).…”

“…However, two of the studies with the lowest frequency are relatively small (NΩ37) (28,29). In line with our results, four previous studies reported (28)(29)(30)(31) that an accumulation of p53 protein is predominantly found in malignant ovarian tumours and rarely in LMPs.…”

“…Relatively few studies have investigated p53 status in epithelial LMPs of the ovary, and the reported frequency varies from 3 to 20% depending on the individual scales of positivity used (28)(29)(30)(31). However, two of the studies with the lowest frequency are relatively small (NΩ37) (28,29). In line with our results, four previous studies reported (28)(29)(30)(31) that an accumulation of p53 protein is predominantly found in malignant ovarian tumours and rarely in LMPs.…”

“…Our overall rate of overexpression (48%) is thus in line with other results. In some studies, p53 staining was found to be significantly associated with FIGO stage (20,32,36), histological grade (18, 20, 28-30, 32, 36), histological type of tumour (29,20) and high patient age (36), whereas others have reported no association with either FIGO stage (18,37,20), histological grade (32), histological type of tumour (18,20) or patient age (18,20). The associations seen between increased p53 levels and later stage disease and serous histology are similar to those reported by Lassus et al (36).…”

“…Relatively few studies have investigated p53 status in epithelial LMPs of the ovary, and the reported frequency varies from 3 to 20% depending on the individual scales of positivity used (28)(29)(30)(31). However, two of the studies with the lowest frequency are relatively small (NΩ37) (28,29).…”