Extracellular matrix alterations in conventional renal cell carcinomas by tissue microarray profiling influenced by the persistent, long-term, low-dose ionizing radiation exposure in humans.
The present study was carried out in order to examine molecular alterations of extracellular matrix (ECM), associated with cell-cell communication in conventional (clear-cell) renal cell carcinomas (cRCCs) influenced by persistent long-term, low-dose ionizing radiation (IR) exposure to patients living more than 19 years after the Chernobyl accident in Cesium 137 (137Cs)-contaminated areas of Ukraine. The ECM major components such as fibronectin, laminin, E-cadherin/beta-catenin complexes and p53 tumor suppressor gene protein, and transforming growth factor beta 1 (TGF-beta1) were immunohistochemically (IHC) evaluated in cRCCs from 59 Ukrainian patients, which represented 18 patients living in non-contaminated areas and 41 patients from 137Cs-contaminated areas. In contrast, a control group of 19 Spanish patients with analogue tumors were also investigated. For IHC evaluation, a tissue microarray technique was used. Decrease or loss and abnormal distribution of fibronectin, laminin, E-cadherin/beta-catenin complexes accompanied by elevated levels of p53 and TGF-beta1 were detected in the Ukrainian cRCCs from 137Cs-contaminated areas with statistically significant differences. Thus, our study suggests that chronic long-term, low-dose IR exposure might result in global remodeling of ECM components of the cRCCs with disruption in peri-epithelial stroma and epithelial basement membranes.
Romanenko
Alina
A
Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, 9a, Yu. Kotzubinsky Street, 04053, Kiev, Ukraine.
Morell-Quadreny
Luisa
L
Ramos
David
D
Nepomnyaschiy
Valentin
V
Vozianov
Alexander
A
Llombart-Bosch
Antonio
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000528:radiation effects; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D047852:Chernobyl Nuclear Accident; D005109:Extracellular Matrix / Q000528:radiation effects*; D005260:Female; D005353:Fibronectins / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D007797:Laminin / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011830:Radiation Effects; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000528:radiation effects
D015820:Cadherins; D005353:Fibronectins; D007797:Laminin; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53