Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma

Ogawa, Shinji; Kaku, Tsunehisa; Kobayashi, Hiroaki; Hirakawa, Tsubasa; Ohishi, Yoshihiro; Kinukawa, Naoko; Nakano, Hitoo

doi:10.1016/s0304-3835(01)00754-6

Cited by 44 publications

(41 citation statements)

References 31 publications

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“…We were unable to detect any stromal deficit in tumors of macrophage-depleted mice, including mature or immature collagen fibers, vascular development, or necrosis. Microvascular density was actually increased in the tumors of these mice, a finding consistent with many patient studies that revealed negative correlations between macrophage density and vascularity in ovarian tumors, and positive correlations between microvascular density and increased progression-free survival (15,(39)(40)(41). A dissociation between angiogenesis and tumor growth has been shown in other contexts (42), and indicates the complexity of the relationship between the tumor stroma and angiogenesis.…”

Section: Discussionsupporting

confidence: 84%

Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice

et al. 2007

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The tumor microenvironment is known to have a profound effect on tumor progression in a highly context-specific manner. We have investigated whether peritoneal inflammation plays a causative role in ovarian tumor metastasis, a poorly understood process. Implantation of human ovarian tumor cells into the ovaries of severe combined immunodeficient mice resulted in peritoneal inflammation that corresponds temporally with tumor cell dissemination from the ovaries. Enhancement of the inflammatory response with thioglycolate accelerated the development of ascites and metastases. Suppression of inflammation with acetyl salicylic acid delayed ascites development and reduced tumor implant formation. A similar prometastatic effect for inflammation was observed when tumor cells were injected directly into the peritoneum of severe combined immunodeficient mice, and in a syngeneic immunocompetent mouse model. Inflammationmodulating treatments did not affect primary tumor development or in vitro tumor cell growth. Depletion of peritoneal macrophages, but not neutrophils or natural killer cells, reduced tumor progression, as assessed by ascites formation and peritoneal metastasis. We conclude that inflammation facilitates ovarian tumor metastasis by a mechanism largely mediated by macrophages, and which may involve stromal vascular endothelial growth factor production. The confirmation of these findings in immunocompetent mice suggests relevance to human disease. Identifying the mechanisms by which macrophages contribute to tumor metastasis may facilitate the development of new therapies specifically targeting immune cell products in the tumor microenvironment. [Cancer Res 2007;67(12):5708-16]

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Section: Discussionsupporting

confidence: 84%

Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice

et al. 2007

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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). Correlation of the cellular proliferation marker index, such as PCNA and Ki-67, with patient survival is also controversial in ovarian cancer (Nakopoulou et al, 1993;Thomas et al, 1995;Itamochi et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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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“…Malignant cells transverse such limitations by accumulating mutations that stoke angiogenic response or by sequestrating circulating growth inhibitors (2). Intratumoral microvascular density is now recognized as an important and independent prognostic marker for metastasis and overall survival in patients with breast, cervical, colon, lung, renal, ovarian, and esophageal carcinomas (3)(4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

Shim

Wong

2007

Molecular Cancer Research

150

111

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Angiopoietins (ANG-1 and ANG-2) and their TIE-2 receptor tyrosine kinase have wide-ranging effects on tumor malignancy that includes angiogenesis, inflammation, and vascular extravasation. These multifaceted pathways present a valuable opportunity in developing novel inhibition strategies for cancer treatment. However, the regulatory role of ANG-1 and ANG-2 in tumor angiogenesis remains controversial. There is a complex interplay between complementary yet conflicting roles of both the ANGs in shaping the outcome of angiogenesis. Embryonic vascular development suggests that ANG-1 is crucial in engaging interaction between endothelial and perivascular cells. However, recruitment of perivascular cells by ANG-1 has recently been implicated in its antiangiogenic effect on tumor growth. It is becoming clear that TIE-2 signaling may function in a paracrine and autocrine manner directly on tumor cells because the receptor has been increasingly found in tumor cells. In addition, A 5 B 1 and A v B 5 integrins were recently recognized as functional receptors for ANG-1 and ANG-2. Therefore, both the ligands may have wide-ranging functions in cellular activities that affect overall tumor development. Collectively, these TIE-2 -dependent and TIE-2 -independent activities may account for the conflicting findings of ANG-1 and ANG-2 in tumor angiogenesis. These uncertainties have impeded development of a clear strategy to target this important angiogenic pathway. A better understanding of the molecular basis of ANG-1 and ANG-2 activity in the pathophysiologic regulation of angiogenesis may set the stage for novel therapy targeting this pathway. (Mol Cancer Res 2007;5(7):655 -65)

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Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma

Cited by 44 publications

References 31 publications

Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice

Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice

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

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

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