VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection

Engels, Knut; Bois, Andreas du; Harter, Philipp; Fisseler‐Eckhoff, Annette; Kommoss, Friedrich; Stauber, R; Kaufmann, M; Nekljudova, Valentina; Loibl, Sibylle

doi:10.1136/jcp.2008.063859

Cited by 31 publications

(25 citation statements)

References 40 publications

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“…19 Improved progression-free survival has been described in patients with iNOS-negative ovarian tumors. [21][22][23] In our study, we found high iNOS expression in both type I and II tumors, but with a significantly higher frequency in the latter group. However, iNOS expression did not stand as an independent prognostic marker when other factors were analyzed.…”

Section: Recently Kurman Et Al Proposed a New Classification Ofsupporting

confidence: 59%

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: Recently Kurman Et Al Proposed a New Classification Ofsupporting

confidence: 59%

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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“…Others have reported that the elevated expression of VEGF in the tumour of EOC patients is associated with poor prognosis [21,26,28,29]. Whilst VEGF has been shown to be a prognostic factor in EOC, this study adds to the field by correlating VEGF status specifically with platinum treatment response.…”

Section: Discussionmentioning

confidence: 86%

Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer

et al. 2011

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“…8 The amount of VEGF-A expressed by tumor cells correlates with poor prognosis in many types of tumors including lung, gastric, colon, prostate, ovary and melanoma. [9][10][11][12][13][14] Of the 3 closely related members of the VEGFR family (VEGFR1, 2, 3), VEGFR2 (also named as KDR or Flk1) and VEGFR3 mainly expressed in vascular and lymphatic endothelial cells, plays major roles in VEGF-A and VEGF-C induced angiogenesis and lymphangiogenesis. 15,16 Binding VEGF ligands to the extracellular domain of VEGFRs on the cell surface of the endothelial cells leads to dimerization of the receptor, and consequently, phosphorylation of the intracellular kinase domain of VEGFRs and triggers activation of downstream cell signaling cascades, including PI3K/AKT, PKC, Raf/Ras and ERK pathways, resulting in vascular/lymphatic endothelial cell proliferation and formation of new vessel branches.…”

Section: Introductionmentioning

confidence: 99%

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

Sun¹,

Zhou²,

Zhang³

et al. 2014

Cancer Biology & Therapy

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VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection

Abstract: VEGF-A and i-NOS are prognostic markers for clinical outcome in serous ovarian cancer patients with macroscopic complete tumour resection (R0). Hence, pre-therapeutic assessment of VEGF-A as predictive factor for an antiangiogenic therapy might be of clinical value.

Cited by 31 publications

References 40 publications

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

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