Clinical significance of p21(WAF1/CIP1) and p53 expression in serous cystadenocarcinoma of the ovary.
ABSTRACT There have been many reports indicating that the down-regulation of p21(WAF1/CIP1) is related to carcinogenesis and the development of various tumors; nevertheless, its association with epithelial ovarian cancer (EOC) remains controversial. In this study, we focused on serous ovarian cancer, which is the most prevalent histological type, and performed immunohistochemical analysis to examine the expression of p21(WAF1/CIP1) and p53 in 43 cases of serous-type EOC sourced from a single University Hospital: 14 stage I, 4 stage II, 21 stage III, and 4 stage IV. Positive p21(WAF1/CIP1) was found in 24 of 43 cases (56%), and positive p53 was detected in 21 of 43 cases (49%). Among stage III/IV cases, positive p21(WAF1/CIP1) staining was found in 11 of 25 cases (44%), and positive p53 staining was detected in 13 of 25 cases (52%). Univariate survival analysis for the entire cohort revealed that positive p21(WAF1/CIP1) was associated with a survival benefit. The 10-year survival rates of p21(WAF1/CIP1)-positive staining and p21(WAF1/CIP1)-negative staining were 82.4 and 39.5%, respectively, and there was a significant difference between the two groups (p<0.01). Overall survival for p21(WAF1/CIP1)-positive with p53-negative staining [p21(+)/p53(-)] was significantly different from p21(WAF1/CIP1)-positive with p53-positive [p21(+)/p53(+)], p21(WAF1/CIP1)-negative with p53-positive staining [p21(-)/p53(+)], and p21(WAF1/CIP1)-negative with p53-negative staining [p21(-)/p53(-)] (p<0.05). When only III/IV cases were evaluated, overall survival for [p21(+)/p53(-)] was significantly different from [p21(+)/p53(+)], [p21(-)/p53(+)], and [p21(-)/p53(-)] (p<0.05). These results suggested that the overexpression of p21(WAF1/CIP1) in conjunction with the loss of p53 expression was a stronger predictor of survival benefit than either molecule alone in Japanese serous-type advanced ovarian cancers with more than 10-year follow-up.
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ABSTRACT: Ovarian cancer is characterized by the highest mortality rate among gynecologic malignancies. Therefore, there is a growing need for innovative therapies and techniques for monitoring and prevention of this disease. The exact cause of most ovarian tumors usually remains unknown. Ovarian cancer is believed to be caused by a range of different variables. This review is an attempt to summarize some genetic factors involved in the disruption of certain signaling pathways responsible for ovarian tumor transformation and development. Those factors considerably contribute to accurate diagnostics, treatment and prognosis in ovarian cancer.Frontiers in Bioscience 01/2013; 18:543-63. · 4.25 Impact Factor
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ABSTRACT: P53, EGFR and HER-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance. Published studies that investigated the association between p53, EGFR and HER-2/neu status and survival were identified. Meta-analysis was performed using a DerSimonian-Laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis. A total of 62 studies were included for p53, 15 for EGFR and 20 for HER-2/neu. P53, EGFR and HER-2/neu status had a modest effect on overall survival (pooled HR 1.47, 95% CI 1.33-1.61 for p53; HR 1.65, 95% CI 1.25-2.19 for EGFR and HR 1.67, 95% CI 1.34-2.08 for HER-2/neu). Meta-regression analysis for p53 showed that FIGO stage distribution influenced study outcome. For EGFR and HER-2/neu, considerable publication bias was present. Although p53, EGFR and HER-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies.British Journal of Cancer 07/2009; 101(1):149-59. · 5.08 Impact Factor
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ABSTRACT: Serous epithelial ovarian tumors can be subdivided into benign (BOV), low malignant potential (LMP) or borderline and invasive (TOV) tumors. Although the molecular characteristics of serous BOV, LMP and low grade (LG) TOV tumors has been initiated, definitive immunohistochemical markers to distinguish between these tumor types have not been defined. In the present study, we used a tissue array composed of 27 BOVs, 78 LMPs and 23 LG TOVs to evaluate the protein expression of a subset of selected candidates identified in our previous studies (Ape1, Set, Ran, Ccne1 and Trail) or known to be implicated in epithelial ovarian cancer disease (p21, Ccnb1, Ckd1). Statistically significant difference in protein expression was observed for Ccnb1 when BOV tumors were compared to LMP tumors (p = 0.003). When BOV were compared to LG TOV tumors, Trail was significantly expressed at a higher level in malignant tumors (p = 0.01). Expression of p21 was significantly lower in LG tumors when compared with either BOVs (p = 0.03) or LMPs (p = 0.001). We also observed that expression of p21 was higher in LMP tumors with no (p = 0.02) or non-invasive (p = 0.01) implants compared to the LMP associated with invasive implants. This study represents an extensive analyse of the benign and highly differentiated ovarian disease from an immunohistochemical perspective.BMC Cancer 12/2008; 8:346. · 3.32 Impact Factor