Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: Correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival

Ali-Fehmi, Rouba; Morris, Robert T.; Bandyopadhyay, Sudeshna; Che, Mingxin; Schimp, Veronica; Malone, John M.; Munkarah, Adnan

doi:10.1016/j.ajog.2004.10.587

Cited by 47 publications

(44 citation statements)

References 20 publications

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“…Of those patients, 118 had already been included in a study published by the authors examining the role of COX-2 in EOC. 10 For uniformity, immunohistochemical staining with COX-2 was repeated on those patients for the current study. Only borderline tumors with micropapillary pattern were included because they are believed to be the precursors of low-grade serous carcinomas, an integral component of type I tumors.…”

Section: Methodsmentioning

confidence: 99%

“…1A-E). 10 For NFjB and Glut-1, the positive control was a section of breast carcinoma, whereas for COX-1, COX-2, and iNOS, the positive controls were sections of esophagus, colon, and lung cancer, respectively. Negative controls consisted of sections that underwent similar staining procedures without the addition of sera.…”

Section: Original Article 302mentioning

confidence: 99%

“…Evidence from in vitro and in vivo studies suggests an important role for prostaglandins and their synthesizing enzyme COX-2 in carcinogenesis. 10 One study investigated the expression of both COX-1 and COX-2 isozymes in normal and malignant ovarian epithelium. 25 COX-1 and COX-2 proteins were present in 69.3% and 70.8%, respectively, of all tumors studied.…”

Section: Recently Kurman Et Al Proposed a New Classification Ofmentioning

confidence: 99%

“…Evidence from in vitro and in vivo studies suggests an important role for prostaglandins and their synthesizing enzyme COX-2 in carcinogenesis. 10 NF-jB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a nuclear transcription factor involved in inflammation. 11 Incorrect regulation of NF-jB has been linked to cancer.…”

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confidence: 99%

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Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P ¼.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P ¼.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P ¼.005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011;117:301-9.

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Section: Methodsmentioning

confidence: 99%

Section: Original Article 302mentioning

confidence: 99%

Section: Recently Kurman Et Al Proposed a New Classification Ofmentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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“…These include an increase in proliferation, reduction in apoptosis, promotion of angiogenesis, modulation in inflammation and immune function, decrease in E-cadherin expression, and stimulation in the invasive/metastatic potential [23]. Studies have demonstrated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of human cancers.…”

Section: Discussionmentioning

confidence: 99%

Expression of COX-2 and Bcl-2 in primary fallopian tube carcinoma: correlations with clinicopathologic features

Wang¹,

Sun²,

Zou³

et al. 2011

Folia Histochem Cytobiol.

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Prognostic significance of cyclooxygenase‐2 in cervical cancer: A meta‐analysis

Huang

Chen

Xiao

et al. 2012

Intl Journal of Cancer

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Published data on the prognostic value of cyclooxygenase-2 (COX-2) overexpression in cervical cancer are conflicting and heterogeneous. We performed a meta-analysis to more precisely estimate its prognostic significance. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effects. Twenty-three studies with 1,477 cervical cancer patients were selected to evaluate the association between COX-2 and overall survival (OS), disease-free survival (DFS), response to chemoradiation (RC) and clinicopathological parameters. High COX-2 expression predicted poor OS (HR: 2.53, 95% CI: 1.54-4.18), DFS (HR: 2.41, 95% CI: 1.58-3.69) and RC (OR: 3.03, 95% CI: 1.97-4.64). Subgroup analyses showed that COX-2 overexpression was related significantly with poor OS in patients treated by chemoradiation or surgery, and in patients with squamous cell carcinoma, respectively. Besides, COX-2 overexpression was related significantly with poor DFS in chemoradiation subgroup. Furthermore, COX-2 overexpression was associated with poor RC in patients who received ''FP'' regimen or ''P'' regimen. Additionally, there were significant associations between COX-2 expression and all clinicopathological parameters except tumor grade. The pooled ORs (95% CI) were as follows: 1.49 (1.09-2.04) for age, 1.77 (1.22-2.56) for lymph node metastasis, 1.04 (0.74-1.47) for tumor grade, 1.71 (1.12-2.64) for tumor size, 2.38 (1.28-4.45) for FIGO stage, 3.96 (2.32-6.77) for histological type, 2.45(1.10-5.42) for parametrical involvement. This meta-analysis indicated that COX-2 overexpression might be an unfavorable prognostic and a chemoradiation resistance predictive factor for cervical cancer; it could potentially help to stratify patients further in clinical treatment.Cervical cancer is the second most common cancer in women worldwide and is a leading cause of cancer-related death in women in developing countries. Despite the public health importance of cervical cancer, factors which influence the outcome of these patients are not completely understood. It is valuable to identify molecular predictive markers for the prognosis, which would be helpful in the selection of therapeutic strategies and further improve patient survival for cervical cancer. Multiple biomarkers with potential prognostic value have been evaluated in cervical cancer, such as epidermal growth factor receptor (EGFR), 1,2 Carbonic anhydrase IX (CAIX), 3,4 vascular endothelial growth factor (VEGF) 5,6 and Cyclooxygenase-2 (COX-2), 7,8 however, there remains some controversy. Additionally, coexpression of multiple biomarkers (such as COX-2, VEGF, EGFR) to be a potent poor survival predictor for cervical cancer have also been evaluated. [9][10][11] As one of the two isoforms of the key enzyme in the biosynthesis of prostaglandins, 12 COX-2 plays an important role in tumor progression, such as cell proliferation, apoptosis inhibition, angiogenesis, invasiveness and immunosuppression. [13][14][15] Multiple studies 5,8,[16][17][18][19][2...

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Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: Correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival

Cited by 47 publications

References 20 publications

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Expression of COX-2 and Bcl-2 in primary fallopian tube carcinoma: correlations with clinicopathologic features

Prognostic significance of cyclooxygenase‐2 in cervical cancer: A meta‐analysis

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