Vasohibin-1 is a new predictor of disease-free survival in operated patients with renal cell carcinoma

Background Vasohibin-1 (VASH1) is an endothelium-produced angiogenesis inhibitor. Renal cell carcinoma is highly vascularised, but the significance of endogenous VASH1 in renal cell carcinoma has not been defined. Aims To identify VASH1 expression and its possible relationship with various clinicopathological factors and prognosis in renal cell carcinoma. Methods A retrospective analysis of 122 tumours obtained from 118 consecutive patients with renal cell carcinoma was performed. The expression patterns of VASH1, CD31, vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2) were examined immunohistochemically and their relationships with clinicopathological factors were analysed. Results Microvessel density, VASH1 and VEGFR2 expression were significantly higher in clear cell carcinoma than in other subtypes. The VEGF expression pattern differed significantly between clear cell carcinoma and other histological subtypes. VASH1, pT factor and TNM stage were significantly associated with disease-free survival (p=0.030, p = 0.0012 and p = 0.0018, respectively). Cox models of multivariable disease-free survival analyses indicated that VASH1 and stage are independent prognostic factors (p=0.019 and p = 0.024). Conclusions VASH1 expression may be useful for estimating the prognosis of renal cell carcinoma. Further studies of the role of VASH1 in renal cell carcinoma involving larger sample sizes are warranted.

[1]  Yan Sun,et al.  Reduced expression of vasohibin-1 is associated with clinicopathological features in renal cell carcinoma , 2012, Medical Oncology.

[2]  Y. Okada,et al.  The Prognostic Significance of Vasohibin-1 Expression in Patients with Upper Urinary Tract Urothelial Carcinoma , 2012, Clinical Cancer Research.

[3]  Yasufumi Sato The vasohibin family: Novel regulators of angiogenesis. , 2012, Vascular pharmacology.

[4]  T. Fujioka,et al.  Brain-specific angiogenesis inhibitor 1 is a putative factor for inhibition of neovascular formation in renal cell carcinoma. , 2011, The Journal of urology.

[5]  H. Sasano,et al.  Roles of intrinsic angiogenesis inhibitor, vasohibin, in cervical carcinomas , 2011, Cancer science.

[6]  H. Sasano,et al.  Vasohibin‐1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast , 2010, Cancer science.

[7]  Gyan Bhanot,et al.  Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. , 2010, Genes & cancer.

[8]  T. Shinka,et al.  Angiogenesis in renal cell carcinoma: The role of tumor‐associated macrophages , 2009, International journal of urology : official journal of the Japanese Urological Association.

[9]  O. Tawfik,et al.  Prognostic significance of CD44, platelet-derived growth factor receptor alpha, and cyclooxygenase 2 expression in renal cell carcinoma. , 2009, Archives of pathology & laboratory medicine.

[10]  T. Shimosegawa,et al.  Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis. , 2009, Blood.

[11]  H. Sasano,et al.  Vasohibin‐1 in human breast carcinoma: A potential negative feedback regulator of angiogenesis , 2009, Cancer science.

[12]  N. Yaegashi,et al.  Expression of vasohibin as a novel endothelium‐derived angiogenesis inhibitor in endometrial cancer , 2008, Cancer science.

[13]  R. Montironi,et al.  Prognostic Role of Tumor Necrosis, Microvessel Density, Vascular Endothelial Growth Factor and Hypoxia Inducible Factor-1α in Patients with Clear Cell Renal Carcinoma after Radical Nephrectomy in a Long Term Follow-up , 2008, International journal of immunopathology and pharmacology.

[14]  F. Goze,et al.  Relation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinoma , 2008, BJU international.

[15]  Francesca Demichelis,et al.  Automated immunofluorescence analysis defines microvessel area as a prognostic parameter in clear cell renal cell cancer. , 2007, Human pathology.

[16]  K. Grankvist,et al.  Evaluation of CD31 (PECAM-1) Expression Using Tissue Microarray in Patients with Renal Cell Carcinoma , 2007, Tumor Biology.

[17]  R. Montironi,et al.  Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens. , 2005, The Journal of urology.

[18]  T. Oda,et al.  Expression and localization of mRNAs for matrix metalloproteinases and their inhibitors in mixed bronchioloalveolar carcinomas with invasive components , 2005, Modern Pathology.

[19]  T. Shuin,et al.  Levels of angiogenesis and expression of angiogenesis‐related genes are prognostic for organ‐specific metastasis of renal cell carcinoma , 2005, Cancer.

[20]  Manuel Hidalgo,et al.  Matrix metalloproteinase-2 contributes to cancer cell migration on collagen. , 2005, Cancer research.

[21]  M. Egawa,et al.  Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma , 2004, International journal of urology : official journal of the Japanese Urological Association.

[22]  M. Abe,et al.  Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. , 2004, The Journal of clinical investigation.

[23]  Sun-Ja Kim,et al.  Increased expression of caveolin‐1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma , 2004, BJU international.

[24]  T. Ochiya,et al.  Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. , 2003, Biochemical and biophysical research communications.

[25]  S. Baltacı,et al.  Thrombospondin-1, vascular endothelial growth factor expression and microvessel density in renal cell carcinoma and their relationship with multifocality. , 2003, European urology.

[26]  M. Marberger,et al.  Expression of platelet-derived growth factor-alpha alpha receptor is associated with tumor progression in clear cell renal cell carcinoma. , 2003, American journal of clinical pathology.

[27]  M. Nishikido,et al.  Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[28]  Holger Moch,et al.  VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma , 2002, The Journal of pathology.

[29]  S. J. Lee,et al.  Clinical significance of urinary vascular endothelial growth factor and microvessel density in patients with renal cell carcinoma. , 2001, Urology.

[30]  H. Radzun,et al.  Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomas , 2001, Virchows Archiv.

[31]  N. Rioux-Leclercq,et al.  Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma. , 2001, Human pathology.

[32]  N. Kawata,et al.  Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: The influence of neoadjuvant treatment , 2001, International journal of urology : official journal of the Japanese Urological Association.

[33]  W. Kaelin,et al.  The von Hippel-Lindau tumor suppressor gene. , 2001, Experimental cell research.

[34]  E. Sabo,et al.  Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[35]  T. Morita,et al.  Thymidine phosphorylase/platelet-derived endothelial cell growth factor (PD-ECGF) associated with prognosis in renal cell carcinoma , 2001, Urological Research.

[36]  A. El‐Naggar,et al.  Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma. , 2001, The American journal of pathology.

[37]  D. Nicol,et al.  Vascular endothelial growth factor expression is increased in renal cell carcinoma. , 1997, The Journal of urology.

[38]  M. Volm,et al.  Microvessel density and vascular endothelial growth factor expression in human tumors of different localization. , 1996, Oncology reports.

[39]  D. Bostwick,et al.  Microvessel density in renal cell carcinoma: lack of prognostic significance. , 1995, Urology.

[40]  K. Okada,et al.  PROGNOSTIC SIGNIFICANCE OF MICROVESSEL COUNT IN LOW STAGE RENAL CELL CARCINOMA , 1995, International journal of urology : official journal of the Japanese Urological Association.

[41]  T. Sugimura,et al.  Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. , 1994, Cancer research.

[42]  E. Manseau,et al.  Vascular permeability factor mRNA and protein expression in human kidney. , 1992, Kidney international.

[43]  E. Lang Arteriographic assessment and staging of renal-cell carcinoma. Analysis of a series of 120 patients. , 1971, Radiology.

[44]  G. Netto,et al.  The relationship of vascular endothelial growth factor and coagulation factor (fibrin and fibrinogen) expression in clear cell renal cell carcinoma. , 2010, Urology.

[45]  Yasufumi Sato,et al.  The vasohibin family: a negative regulatory system of angiogenesis genetically programmed in endothelial cells. , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[46]  Ricky T. Tong,et al.  Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor beta signaling inhibits human renal cell carcinoma progression in an orthotopic mouse model. , 2005, Cancer research.

[47]  M. Marberger,et al.  Expression of platelet-derived growth factor-alpha alpha receptor is associated with tumor progression in clear cell renal cell carcinoma. , 2003, American journal of clinical pathology.

[48]  E. Lang Arteriographic assessment and staging of renal cell carcinoma. , 1976, Panminerva medica.