Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas

Abstract

Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

A novel immunohistochemical method for estimating cell cycle phase distribution in ovarian serous neoplasms: implications for the histopathological assessment of paraffin-embedded specimens

“…The findings we describe for Mcm-2 are similar to those obtained in previous studies using Ki67 (Garzetti et al, 1995;Blegen et al, 2000). Indeed, it has been shown previously that tumour cell proliferation, as assessed by the Ki67 LI, was significantly higher in cases of serous ovarian cystadenocarcinoma that recurred or progressed than in those that did not (Garzetti et al, 1995).…”

Gross genomic alterations differ between serous borderline tumors and serous adenocarcinomas—an image cytometric DNA ploidy analysis of 307 cases with histogenetic implications

“…There are different opinions concerning the histogenesis of serous ovarian tumors, some supporting a progression from SBT to SAC [8,10] and others favoring a dualistic model [5,[11][12][13][14]. We studied this issue using high-resolution DNA ploidy image analysis in different subgroups of SBT and grades of SAC in a large and well-characterized retrospective material.…”

Serum and tissue biomarkers as predictive and prognostic variables in epithelial ovarian cancer

“…Cyclin E is overexpressed in 18-70% of EOCs, and is more often detected in clear cell carcinoma than in other histological types [74,84,94,[104][105][106][107][108][109][110][111] (Table 3(b)). Most authors showed that high-cyclin E expression represents a poor prognostic variable [84,94,106,107,109,111,112].…”

“…Most authors showed that high-cyclin E expression represents a poor prognostic variable [84,94,106,107,109,111,112]. For instance, Sui et al [107] reported a lower survival in women who had cyclin E overexpression than in those who had not.…”