Microvessel density is high in clear-cell renal cell carcinomas of Ukrainian patients exposed to chronic persistent low-dose ionizing radiation after the Chernobyl accident

Abstract

During the 25-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in Ukraine has increased from 4.7 to 10.7 per 100,000 of the total population. Recent studies of our group have shown that increases in morbidity, aggressiveness, and proliferative activity of renal cell carcinomas (RCCs), especially clear-cell renal cell carcinoma (CCRCC), in Ukrainian patients continuously inhabiting the radio-contaminated areas could be explained by specific molecular changes influenced by the so-called "chronic persistent low-dose ionizing radiation" (CPLDIR) exposure. This study aimed to examine the role of angiogenesis in CCRCC carcinogenesis associated with CPLDIR in patients living more than 20 years in cesium 137 ((137)Cs) contaminated areas after the Chernobyl accident in Ukraine. Paraffin-embedded specimens of 106 CCRCs were studied: Control cases were 18 tumors from Spanish patients (group 1), 25 tumors from Ukrainian patients from so-called clean areas without known radio-contamination (group 2), and 63 tumors from Ukrainian patients from radio-contaminated areas (group 3). For intratumoral microvessel density (MVD) determination, anti-CD31 antibody was used. A computerized image analysis program was used to quantitatively calculate the vascular density. Seventy-three percent of group 3 and 72 % of group 2 CCRCCs displayed the highest MVD. A striking increase in MVD was seen in group 3 CCRCCs, in comparison with groups 1 and 2 (p < 0.001). The majority of the hot spot vessels in group 3 was poorly differentiated. Moreover, MVD values for total vessels as well as for capillaries and tumor grade were strongly correlated. When we compared only tumor-node-metastasis tumor stages I and II, the differences remained statistically significant (p < 0.1). The ratio of the average total vessels and capillaries in the Ukrainian groups combined was 1.65:1 in comparison to the Spanish group. Our results provide evidence that CPLDIR exposure increases MVD (particularly capillary) in CCRCCs and is associated with a higher histological grade.

Malignancies after Chernobyl Accident: What Is True and What Is Untrue

“…It was reported that in 73 % of RCC patients from contaminated territories and 72 % of patients from noncontaminated areas of Ukraine, the tumor displayed a relatively high level of microvessel density: the average density in both Ukrainian groups combined was 1.65 times higher than in a control group from Spain [55]. Radiation exposure was put in connection with tumor dedifferentiation [55]. An association of microvessel density with the grade of RCC had been also reported previously [59,60].…”

“…Furthermore, the following was pointed out: "The strong significant differences between the Ukrainian and Spanish groups were found in tumoral nuclear grade" [57] and "Our data showed in the majority of Ukrainian patients a radiation sclerosing proliferative atypical nephropathy in association with an increase in the incidences of tubular epithelial nuclear atypia and carcinoma in situ" [58]. It was reported that in 73 % of RCC patients from contaminated territories and 72 % of patients from noncontaminated areas of Ukraine, the tumor displayed a relatively high level of microvessel density: the average density in both Ukrainian groups combined was 1.65 times higher than in a control group from Spain [55]. Radiation exposure was put in connection with tumor dedifferentiation [55].…”

“…For example, the statement: "During the 25-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in Ukraine has increased from 4.7 to 10.7 per 100,000 of the total population" [55] was supported by a reference to a report by the Ministry of Health of Ukraine. However, the incidence increase of renal cell carcinoma (RCC) due to the Chernobyl fallout has never been proven scientifically; some increase could have been caused by improved diagnostics [56].…”

A New Conversation between Radiology and Pathology-Identifying Microvascular Architecture in Stages of Cirrhosis via Diffraction Enhanced Imaging In Vitro

“…Subsequently, the microvascular density (MVD) was determined by two pathologists, independently and in masked trials, on 10 non-overlapping areas at 200× magnification. Only immune-positive clusters of cells with a lumen were considered as individual vessels for the purposes of microvessel counting, consistent with the procedures described by Romanenko [16]. Vascular density was expressed as…”

Development and Validation of a Histological Method to Measure Microvessel Density in Whole-Slide Images of Cancer Tissue

“…Hitherto, microvessel counting has mostly been performed in a fraction of the total tissue area determined by a sampling method such as the vascular hotspot method (Weidner’s method). This method involves the selection of one to five areas with the highest density of microvessels (hotspots) at low magnification, and the counting of vessels in these areas at high magnification [14,15] by computerized image analysis systems [16,17] or by applying a Chalkley grid [18]. In a previous study, we used a systematic uniform random sampling (SURS) method to avoid observer-dependent sampling variation and selected a limited number of at least five regions of interest (ROIs) on each whole-slide image (WSI) [19].…”