Prognostic significance of tumor angiogenesis in epithelial ovarian cancer

Obermair, Andreas; Wasicky, R.; Kaider, Alexandra; Preyer, Oliver; Lösch, Alexander; Leodolter, Sepp; Kölbl, H.

doi:10.1016/s0304-3835(99)00005-1

Cited by 41 publications

(27 citation statements)

References 20 publications

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“…Previous studies showed that MVD was not a useful prognostic factor in ovarian cancer (Obermair et al, 1999;Shen et al, 2000;Bamberger and Perrett, 2002). On the other hand, Hollingsworth et al (1995) reported that MVD was significantly correlated with poor prognosis of advanced stage ovarian cancer, while conversely it was associated with better prognosis (Ogawa et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival

et al. 2006

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Angiotensin II, a main effector peptide in the renin -angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT 1 R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT 1 R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT 1 R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT 1 R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n ¼ 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT 1 R, the overall survival and progression-free survival were significantly poor (P ¼ 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT 1 R, although VEGF, but not AT 1 R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT 1 R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.

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Section: Discussionmentioning

confidence: 97%

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival

et al. 2006

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“…These observations may be explained by the fact that higher tumor vascularity might permit better drug and oxygen availability, resulting in a therapeutic benefit, whereas tumor hypoxia leads to a poor response to chemotherapy (12). On the other hand, some investigators have found that MVD has no prognostic significance in ovarian cancer patients (13,14,23), possibly reflecting the hypothesis that new vessels formed in association with angiogenesis have structural and functional abnormalities with chaotic flow and intermittent stagnation, making it difficult to deliver drugs uniformly throughout the tumor (24). Thus, the role of angiogenesis in ovarian cancer prognosis and response to therapy remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Differences in Prognostic Molecular Markers between Women Over and Under 45 Years of Age with Advanced Ovarian Cancer

Chan

Loizzi

Magistris

et al. 2004

Clinical Cancer Research

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Purpose: The purpose of this study was to determine whether differences in molecular markers might explain the better prognosis of women <45 years of age versus women >45 years of age diagnosed with ovarian cancers.Experimental Design: Tissue sections from women with stage III-IV ovarian cancers were examined for expression of CD34, p53, and HER2. The Kaplan-Meier method and Cox Proportional Hazard analyses were used to identify predictors for outcome.Results: Fifty-two women <45 years of age were matched with 52 women who were >45 years old. Of the 46 available tissue sections, 24 were from the younger age group (mean age, 41 years), and 22 were from the older age group (mean age, 61 years). Based on CD34 expression, tumors from women >45 years of age had lower microvessel density (MVD) compared with tumors of younger women (10.3 versus 16.1 microvessels per ؋400 field; P ‫؍‬ 0.03). Lower MVD (<11 microvessels per ؋400 field) predicted for a worse prognosis than higher MVD (>11 microvessels per ؋400 field) in the overall study group (P ‫؍‬ 0.001) and within the older subgroup (P ‫؍‬ 0.03). The expressions of p53 (P ‫؍‬ 0.13) and HER2 (P ‫؍‬ 0.49) did not vary between the two age groups. The median survivals of those with tumors that overexpressed p53 and HER2 were 28.6 and 23.9 months compared with 51.7 and 38.6 months in those with cancers that underexpressed these markers, respectively (P ‫؍‬ 0.09 for p53, P ‫؍‬ 0.15 for HER2).Conclusions: Ovarian cancers in women >45 years of age had lower MVD compared with those in women <45 years of age. Lower MVD was an independent prognostic factor for decreased survival. Lower frequency of neovascularization in these cancers may contribute to the decreased survival observed in women >45 years of age.

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“…41 In ovarian carcinomas, several studies have shown that microvessel density is not an independent prognostic indicator. [42][43][44] Therefore, we did not measure microvessel density in the present study. Similarly, it has been shown that the apoptotic index is no independent prognostic indicator in ovarian carcinomas.…”

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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Prognostic significance of tumor angiogenesis in epithelial ovarian cancer

Cited by 41 publications

References 20 publications

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival

Differences in Prognostic Molecular Markers between Women Over and Under 45 Years of Age with Advanced Ovarian Cancer

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

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