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.

Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation

“…; Ruiz‐Saurí et al. ). The images were transformed to grayscale, calibrated to 20×, and segmented around the stained cell of interest in order to count them individually.…”

“…All the images were analyzed using the biomedical image analysis software IMAGE-PRO PLUS 7.0 (Infaimon, Media Cybernetics) to obtain morphometric parameters. The numbers of neurons and each type of glia were measured using a semiautomatic counting protocol (Lejeune et al 2008;Ruiz-Saur ı et al 2016). The images were transformed to grayscale, calibrated to 209, and segmented around the stained cell of interest in order to count them individually.…”

Markers of Radiogenic Cancer vs. Tumor Progression: an Overview of Chernobyl Studies

“…Studies of Chernobyl-related clear-cell renal-cell carcinoma (RCC) with a control from other countries are discussed here in comparison with thyroid cancer (TC). The series of studies [4][5][6][7][8][9][10], in particular, the last study [10], compared RCC tissue specimens from Ukraine (including the area of Chernobyl contamination) with those from Spain and Colombia. In brief, RCCs from Ukraine tended to be less differentiated than the overseas controls [4][5][6][7][8][9][10].…”

“…The series of studies [4][5][6][7][8][9][10], in particular, the last study [10], compared RCC tissue specimens from Ukraine (including the area of Chernobyl contamination) with those from Spain and Colombia. In brief, RCCs from Ukraine tended to be less differentiated than the overseas controls [4][5][6][7][8][9][10]. In the last study, the microvessel density in the RCC tissue from patients residing both in "highly" and in "low contaminated areas of Ukraine" was considerably higher than in RCC from Spain and Colombia (p<0.01).…”

Chernobyl cancer studies with overseas control: high grade vs. late detection

“…Annual average doses from the natural radiation background should be indicated in the studies comparing patients from different countries; otherwise doses in controls may turn out to be not significantly different from those in the "exposed" group. No doses are given in the articles (2)(3)(4)(5)(6)(7). Individual effective doses from the natural background are generally expected to range from 1.0 to 10 mSv/year; some national averages exceed 10 mSv/year (9,10).…”