title: Influence of Exposure to Chronic Persistent Low-Dose Ionizing Radiation on the Tumor Biology of Clear-Cell Renal-Cell Carcinoma. An Immunohistochemical and Morphometric Study of Angiogenesis and Vascular Related Factors.
abstract: Increased angiogenesis is related to boosted growth and malignancy in carcinomas. "Chronic Persistent Low-Dose Ionizing Radiation" (CPLDIR) exposure increases incidence and aggressive behavior of clear-cell renal-cell carcinoma (CCRCC). The aim was to study the biology of angiogenesis, including microvessel density (MVD), in human clear-cell renal-cell carcinomas (CCRCC) originating from a radio-contaminated geographical area (Ukraine) and to compare with similar tumors diagnosed in non-contaminated regions of Europe (Spain, Valencia) and Latin America (Colombia, Barranquilla). MVD was comparatively examined in 124 patients diagnosed with CCRCC from three geographical areas by means of digital micro-imaging and computerized analysis. Additionally, 50 adult normal kidneys were used for controls (autopsy kidneys from Valencia and Barranquilla). Furthermore, an immunohistochemical study of several vascular related growth factors was undertaken using a similar methodology. MVD as well as VEFG are the most discriminating factors associated with an aggressive behavior of CCRCC. Their expression increased in proportion to the level of exposure to chronic low-dose ionizing radiation in Ukrainian patients in the 25 years since the Chernobyl accident substantiated by comparison with the two control groups of renal carcinomas present in non-irradiated areas (Spain and Colombia). No major biological differences relating to angiogenesis appear to exist between the CCRCC diagnosed in two distant geographical areas of the world. HIF-1α expression was similar in all groups, with no statistical significance. Present findings demonstrate the existence of a significant relationship between MVD and VEGF in CCRCC: an increased expression of VEGF is associated with a high level of angiogenesis.
authors.affiliation: Department of Pathology, University of Valencia, Avenida Blasco Ibañez, 15, 46010, Valencia, Spain. Amparo.Ruiz-Sauri@uv.es.|INCLIVA Biomedical Research Institute, Valencia, Spain. Amparo.Ruiz-Sauri@uv.es.|Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. Amparo.Ruiz-Sauri@uv.es.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz-Saurí
authors.affiliation: Department of Pathology, University of Valencia, Avenida Blasco Ibañez, 15, 46010, Valencia, Spain.|Universidad del Norte, Medical School, Barranquilla, Colombia.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Valencia-Villa
authors.affiliation: Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine.
authors.forename: Alina
authors.initials: A
authors.lastname: Romanenko
authors.affiliation: Medical School, Universidad Libre, Barranquilla, Colombia.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez
authors.affiliation: Universidad del Norte, Medical School, Barranquilla, Colombia.
authors.forename: Raúl
authors.initials: R
authors.lastname: García
authors.affiliation: Department of legal medicine, Barranquilla, Colombia.
authors.forename: Heydi
authors.initials: H
authors.lastname: García
authors.affiliation: Department of Pathology, University of Valencia, Avenida Blasco Ibañez, 15, 46010, Valencia, Spain.|INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Benavent
authors.affiliation: Department of Pathology, University of Valencia, Avenida Blasco Ibañez, 15, 46010, Valencia, Spain.|INCLIVA Biomedical Research Institute, Valencia, Spain.|Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sancho-Tello
authors.affiliation: Department of Pathology, University of Valencia, Avenida Blasco Ibañez, 15, 46010, Valencia, Spain.|INCLIVA Biomedical Research Institute, Valencia, Spain.|Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Carda
authors.affiliation: Department of Pathology, University of Valencia, Avenida Blasco Ibañez, 15, 46010, Valencia, Spain.|INCLIVA Biomedical Research Institute, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D011839:Radiation, Ionizing; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; C021266:vascular factor
keywords: Angiogenesis; Angiogenic factors; Chronic persistent low-dose ionizing radiation (CPLDIR); Clear-cell renal-cell carcinoma (CCRCC); Immunohistochemistry; Microvessel density (MVD); Morphometry