p53 And related proteins in epithelial ovarian cancer

Sengupta, P S; McGown, Alan T.; Bajaj, Vikram S.; Blackhall, Fiona; Swindell, Ric; Bromley, Michael; Shanks, J H; Ward, Tim; Buckley, C. H.; Reynolds, Karina; Slade, RJ; Jayson, Gordon C

doi:10.1016/s0959-8049(00)00301-4

Cited by 34 publications

(37 citation statements)

References 50 publications

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“…Similarly, it has been shown that the apoptotic index is no independent prognostic indicator in ovarian carcinomas. 45,46 However, in some studies apoptosis-related proteins such as p53, bcl-2, or bax have been shown to affect prognosis of ovarian carcinomas. 46,47 Thus, it will be very interesting to investigate the correlation between COX-2 expression and different factors involved in apoptotic or necrotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma

Denkert

Köbel

Pest

et al. 2002

The American Journal of Pathology

175

137

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Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme in prostanoid biosynthesis and is involved in tumor progression. We investigated expression of COX-1 and COX-2 in cell lines and tumors from ovarian carcinomas. Expression of COX-2 mRNA and protein was detectable in three of five ovarian carcinoma cell lines and was inducible by interleukin-1␤ or phorbolester in a subset of cell lines. Prostaglandin E 2 (PGE 2 ) production could be inhibited by the selective COX-2 inhibitor NS-398. In malignant ascites of ovarian carcinomas significantly increased levels of PGE 2 were found compared to other carcinomas or nonmalignant ascites (P ‫؍‬ 0.03). We investigated expression of COX-2 by immunohistochemistry in 117 ovarian surface epithelial tumors. Expression of COX-2 was detected in 42% of 86 ovarian carcinomas and in 37% of 19 low malignant potential tumors, but not in 12 cystadenomas or 2 normal ovaries. Expression of COX-1 was detected by immunohistochemistry in 75% of 75 invasive ovarian carcinomas and in 75% of 16 low malignant potential tumors, whereas 2 samples from normal ovaries and 8 cystadenomas were positive for COX-1. In univariate survival analysis of invasive carcinomas, expression of COX-2 was associated with a significantly reduced median survival time (log rank test, P ‫؍‬ 0.04). For patients younger than 60 years of age, this association was even more significant (P < 0.004). In contrast, expression of COX-1 was no prognostic parameter (P ‫؍‬ 0.89). There was no significant correlation between COX-2 or COX-1 expression and other clinicopathological markers. In multivariate analysis expression of COX-2 was an independent prognostic factor for poor survival (relative risk, 2.74; 95% CI, 1.38 to 5.47). Our data indicate that COX-2 expression is an independent prognostic factor in ovarian carcinoma. Based on the results of this study, it would be interesting to

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Section: Discussionmentioning

confidence: 99%

Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma

Denkert

Köbel

Pest

et al. 2002

The American Journal of Pathology

175

137

View full text Add to dashboard Cite

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“…In regard to BAX expression, a few studies have addressed the issue of its clinical significance in advanced stage ovarian carcinomas; however, associations with CR or DFS have not been observed (Marx et al, 1997;Baekelandt et al, 2000;Sengupta et al, 2000;Schuyer et al, 2001). Recently, Schuyer et al (2001) found an association of BAX expression with progression-free survival.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

et al. 2003

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In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatinbased chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB -IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P ¼ 0.005) or the only (in FIGO IIIC, P ¼ 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(À) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P ¼ 0.047) and by BCL2 expression in the TP53(À) group (P ¼ 0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P ¼ 0.049); its loss was found with advancing FIGO stage (P ¼ 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

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“…Surgical and pathologic findings and postoperative abdomino-pelvic computerised tomography (CT) scans were used to determine the FIGO stage for the ovarian adenocarcinomas and the residual disease after the initial surgery. Persistence of tumour masses of o2 cm was defined as minimal residual disease, whereas the presence of masses of 42 cm in diameter was defined as bulk residual disease (Anttila et al, 1999;Sengupta et al, 2000). All patients with carcinomas had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by chemotherapy.…”

Section: Study Populationsmentioning

confidence: 99%

Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications

et al. 2007

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Minichromosome maintenance proteins (MCM) have recently emerged as novel proliferation markers with prognostic implications in several tumour types. This is the first study investigating MCM-2 and MCM-5 immunohistochemical expression in a series of ovarian adenocarcinomas and low malignant potential (LMP) tumours aiming to determine possible associations with clinicopathological parameters, the conventional proliferation index Ki-67, cell cycle regulators (p53, p27 Kip1 , p21 WAF1 and pRb) and patients' outcome. Immunohistochemistry was applied in a series of 43 cases of ovarian LMP tumours and 85 cases of adenocarcinomas. Survival analysis was restricted to adenocarcinomas. The median MCM-2 and MCM-5 labelling indices (LIs) were significantly higher in adenocarcinomas compared to LMP tumours (Po0.0001 for both associations). In adenocarcinomas, the levels of MCM-2 and MCM-5 increased significantly with advancing tumour stage (P ¼ 0.0052 and P ¼ 0.0180, respectively), whereas both MCM-2 and MCM-5 increased significantly with increasing tumour grade (P ¼ 0.0002 and P ¼ 0.0006, respectively) and the presence of bulky residual disease (Po0.0001 in both relationships). A strong positive correlation was established between MCM-2 or MCM-5 expression level and Ki-67 LI (Po0.0001) as well as p53 protein (P ¼ 0.0038 and P ¼ 0.0500, respectively). Moreover, MCM-2 LI was inversely correlated with p27KipÀ1 LI (P ¼ 0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients' outcome in both univariate (X20 vs 420%, P ¼ 0.0011 and X25 vs o25%, P ¼ 0.0100, respectively) and multivariate (P ¼ 0.0001 and 0.0090, respectively) analysis. An adequately powered independent group of 45 patients was used in order to validate our results in univariate survival analysis. In this group, MCM-2 and MCM-5 expression retained their prognostic significance (Po0.0001 in both relationships). In conclusion, MCM-2 and MCM-5 proteins appear to be promising as prognostic markers in patients with ovarian adenocarcinomas.

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p53 And related proteins in epithelial ovarian cancer

Cited by 34 publications

References 50 publications

Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma

Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications

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