Immunohistochemical Study of the Angiogenetic Network of VEGF, HIF1α, VEGFR-2 and Endothelial Nitric Oxide Synthase (eNOS) in Human Breast Cancer

Kafousi, Maria; Vrekoussis, Thomas; Tsentelierou, Eleftheria; Pavlakis, Kitty; Navrozoglou, Iordanis; Dousias, Vassilios; Sanidas, Elias; Tsiftsis, D; Georgoulias, V.; Stathopoulos, Efstathios N.

doi:10.1007/s12253-011-9413-8

Cited by 18 publications

(12 citation statements)

References 47 publications

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“…To the best of our knowledge, this is the first survival study investigating the potential prognostic value of VEGFR‐2. In accordance with previous IHC reports in human breast cancer, we did not find any significant relationship between VEGF or VEGFR‐2 expressions and tumour size, lymph node status or patient overall and DFS . Similarly, Millanta et al also reported that VEGF does not influence the survival time of female dogs with MMTs .…”

Section: Discussionsupporting

confidence: 92%

“…In our study, VEGFR‐2 was expressed in the endothelial cells of the intra‐tumoural vasculature and the mammary cancer epithelial cells, while VEGF was mainly detected in the neoplastic cells. As previously described in human and canine mammary tumours, VEGF expression was significantly associated with the presence of VEGFR‐2 in cancer cells, supporting the existence of an autocrine VEGF/VEGFR2 loop . In women breast cancer, it has been postulated that this loop integrates signalling pathways for cancer cell proliferation and resistance to apoptosis .…”

Section: Discussionsupporting

confidence: 67%

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VEGFR‐2 expression in malignant tumours of the canine mammary gland: a prospective survival study

Santos

Lopes

Gärtner

et al. 2014

Vet Comparative Oncology

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Vascular endothelial growth factor receptor-2 (VEGFR-2) is the main receptor activated by vascular endothelial growth factor -A (VEGF-A) to promote tumour angiogenesis. Its clinical prognostic value has not been studied in canine mammary tumours (CMTs). Dogs with mammary cancer were enrolled in a survival study and the immunohistochemical expressions of VEGFR-2 and VEGF-A were analysed and associated with clinicopathological features. VEGFR-2 expression was associated with VEGF immunoreactivity in cancer cells, supporting the presence of an autocrine loop that may be involved in CMTs growth and survival. VEGFR-2 was also expressed by endothelial cells from tumour vasculature and positively associated with stromal matrix metalloproteinase-9 (MMP-9), suggesting the existence of a link between endothelial cells activation and up-regulation of matrix degrading proteins. Carcinosarcomas exhibited high VEGFR-2 expression suggesting that it may be one of the activated molecular pathways in this aggressive histological type and that VEGFR-2 inhibitors may constitute a potential treatment to improve the prognosis of these patients. Both VEGF and VEGFR-2 immunoreactivities were independent of patients' overall survival (OS) and disease-free survival (DFS).

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 67%

VEGFR‐2 expression in malignant tumours of the canine mammary gland: a prospective survival study

Santos

Lopes

Gärtner

et al. 2014

Vet Comparative Oncology

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“…Positive staining (3+) for Her-2 corresponded to strong staining in >30% of tumor cells, whereas weak to moderate staining in >10% cells was scored as equivocal (2+), and no staining or faint incomplete staining was scored as negative (−) or faint (1+)20. For VEGF staining, intensity of cytoplasmic immunostaining was scored from 0 to 3+ (no staining to strong staining, respectively)21. Vimentin, AACT, desmin, S-100, CK, EMA, CD68 or CD163 staining was considered positive if cell staining was either in the cytoplasm, membrane, or nucleus.…”

Section: Methodsmentioning

confidence: 99%

Diagnostic and therapeutic strategy and the most efficient prognostic factors of breast malignant fibrous histiocytoma

Qiu

Wei

Huang

et al. 2013

Sci Rep

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We analyzed the clinicopathological features of 9 breast malignant fibrous histiocytoma (MFH) patients. Immunohistochemistry was used to make both diagnosis and differential diagnosis, and to identify prognostic factors. All tumors lacked epithelial markers but expressed mesenchymal markers, suggesting a mesenchymal origin. Of the five cases expressing Ki-67, two of three patients with axillary lymph node involvement died between 6–8 months, and two died at 17 and 26 months after diagnosis. The two remaining cases, with low Ki-67 expression, had no recurrent or metastatic disease at 145 months after diagnosis. Previous studies have shown that surgery is the primary treatment of choice, but no clear benefit from adjuvant chemotherapy was observed. We demonstrate that axillary lymph node involvement and high expression of Ki-67 are associated with poorer prognosis. A literature review indicates surgery remains the first choice for MFH, but benefits from adjuvant chemotherapy remain unclear.

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“…AKT1-knockout mice showed impaired vascular maturation with decreased expression of TSP-1 and TSP-2, while reexpression of TSP-1 and TSP-2 in mice transplanted with wild-type bone marrow is associated with the angiogenesis [39]. The endothelial NOS (eNOS) is critical for VEGF-triggered postnatal angiogenesis [40, 41]. Several protein kinases, such as Akt, AMP-activated protein kinase (AMPK), and protein kinase A (PKA), are known to activate eNOS [42].…”

Section: Downstream Molecules Mediated By Pi3k/akt/pten In Regulatmentioning

confidence: 99%

PI3K/AKT/PTEN Signaling as a Molecular Target in Leukemia Angiogenesis

Okumura

Yoshida

Kitagishi

et al. 2012

Advances in Hematology

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PI3K/AKT/PTEN pathway is important in the regulation of angiogenesis mediated by vascular endothelial growth factor in many tumors including leukemia. The signaling pathway is activated in leukemia patients as well as leukemia cell lines together with a decrease in the expression of PTEN gene. The mechanism by which the signaling pathway regulates angiogenesis remains to be further elucidated. However, it has become an attractive target for drug therapy against leukemia, because angiogenesis is a key process in malignant cell growth. In this paper, we will focus on the roles and mechanisms of PI3K/AKT/PTEN pathway in regulating angiogenesis.

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Immunohistochemical Study of the Angiogenetic Network of VEGF, HIF1α, VEGFR-2 and Endothelial Nitric Oxide Synthase (eNOS) in Human Breast Cancer

Abstract: In breast cancer cases, the major molecules regulating NO and VEGF production can be co-expressed in the individual carcinomas implying a possibility for the relevant pathways to be active; however appropriate functional experiments remain to be conducted to prove such a hypothesis.

Cited by 18 publications

References 47 publications

VEGFR‐2 expression in malignant tumours of the canine mammary gland: a prospective survival study

VEGFR‐2 expression in malignant tumours of the canine mammary gland: a prospective survival study

Diagnostic and therapeutic strategy and the most efficient prognostic factors of breast malignant fibrous histiocytoma

PI3K/AKT/PTEN Signaling as a Molecular Target in Leukemia Angiogenesis

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