High Expression of Vascular Endothelial Growth Factor Predicts Early Recurrence and Poor Prognosis after Curative Resection for Ductal Adenocarcinoma of the Pancreas

Niedergethmann, Marco; Hildenbrand, Ralf; Wostbrock, Birgit; Hartel, Mark; Sturm, J.; Richter, Α.; Post, Stefan

doi:10.1097/00006676-200208000-00002

Cited by 181 publications

(106 citation statements)

References 32 publications

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“…VEGF is upregulated in many human tumours and its expression has usually been correlated with a high microvascular density and poor clinical outcome (Itakura et al, 1997;Seo et al, 2000;Hui et al, 2002;Niedergethmann et al, 2002). In the present study, VEGF expression detected in 78% of PETs, mainly in highly vascularised benign cases, is in accordance with previous results La Rosa et al, 2003).…”

Section: Discussionsupporting

confidence: 91%

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression

et al. 2004

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Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series of patients with pancreatic endocrine tumours (PETs). The expression of vascular endothelial growth factor (VEGF), HIF-1a, HIF-2a and carbonic anhydrase 9 (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density (MVD), endothelial proliferation, tumour stage and survival. Microvascular density was very high in PETs and associated with a low endothelial index of proliferation. Microvascular density was significantly higher in benign PETs than in PETs of uncertain prognosis, well-differentiated and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels mm À2, respectively, Po0.0001). Well-differentiated tumours had high cytoplasmic VEGF and HIF-1a expression. Poorly differentiated carcinomas were associated with nuclear HIF-1a and membranous CA9 expression. Low MVD (P ¼ 0.0001) and membranous CA9 expression (P ¼ 0.0004) were associated with a poorer survival. Contrary to other types of cancer, PETs are highly vascularised, but poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD significantly decreases. The regulation of HIF signalling appears to be specific in pancreatic endocrine tumours.

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Section: Discussionsupporting

confidence: 91%

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression

et al. 2004

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“…28 The correlation between VEGFA expression and the survival remains significant even after a surgery putatively considered as curative. 39 These results are consistent with the discovery that microvessel density and vascular proliferation index were significantly associated with larger tumor size and lymph node metastasis. 40 A recent study demonstrated that focal VEGFA locus amplification is regularly detected in PDAC.…”

Section: Discussionsupporting

confidence: 90%

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

Fahmy

Gonzalez

Arafa

et al. 2015

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.

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“…Our data did not show any correlation between the immunohistochemical expression of VEGF and tumor grade, stage or patients survival. But, such association was reported for tumors of several organs such as prostate 9 , pancreas 10 , lung 11 and colon 12 .…”

Section: Discussionmentioning

confidence: 96%

VEGF immunoexpression in penile carcinoma

et al. 2002

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OBJECTIVE: To investigate the vessel endothelial growth factor (VEGF) as a risk factor in squamous cell carcinoma of the penis (SCCP). METHODS: Forty-seven patients with penile carcinoma were evaluated retrospectively. The mean age and standard deviation were 61.1±11.7 years. All of them were treated by penectomy and those with positive nodes underwent groin lymphadenectomy. Tumor grading was 35 G1 and 12 G2/3. Primary lesion stage was 24 pT1 and 23 pT2-4. Positive inguinal nodes were observed in 15 patients. Selected paraffin embedded sections were submitted to VEGF immunohistochemical analysis by the avidin-biotin-immunoperoxidase method with antigen retrieval. All slides were examined using an automatic analyzer system and the proportion of labeled cells in 10 high magnification power fields (400X) were recorded in a blind analysis. RESULTS: Median (%) labeling index was 2.3 in G1 versus 2.2 in G2/3 tumors (p=0.60), and 4.0 in pT1 versus 1.8 pT2-4 tumors (p=0.10). The respective data for pN0 patients was 2.8 and for pN+ was 2.1 (p=0.20). Survival curves showed no association with patients survival. CONCLUSION: In squamous cell carcinoma of the penis the VEGF immunoexpression has no association with tumor grade or stage, as well as with patient survival

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High Expression of Vascular Endothelial Growth Factor Predicts Early Recurrence and Poor Prognosis after Curative Resection for Ductal Adenocarcinoma of the Pancreas

Cited by 181 publications

References 32 publications

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

VEGF immunoexpression in penile carcinoma

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