clear cell renal carcinoma of different GRADES of differentiation: peculiarity of tumor cells ultrastructure
Keywords:
clear cell renal cell carcinoma, tumoral cell, hyaline globule, glycogen granule, lipid drop, mitochondria.Abstract
Summary. Aim: is to reveal in comparative plan ultrastructural organization of tumor cells (TC) of clear cell renal cell carcinoma (CCRCC) of different grades of differentiation. Object and methods: material for conducting transmission electron microscopic researches was postoperative biopsies of peripheral and central parts of tumors in CCRCC at highly differentiated cancer (G1) — 5 cases; at an average grade of differentiation (G2) — 5 cases; at low grade of differentiation (G3) — 6 cases. The control studies: 1) the biopsies of renal cortex of eliminated parts of the kidney with tumor and the whole kidney with tumor in these patients in CCRCC; 2) biopsies of renal cortex of sexually mature white rats. Results: it was detected that the high, low and average electron density of the TC with the predominance of the last are present in alveoli, tubules and acini of different grades of differentiation at CCRCC in tumors of highly differentiated (G1) at CCRCC. The control studies made it possible to reveal that the ultrastructural organization of epithelial cells with an average electronic density of tumors with a high grade of differentiation (G1) at CCRCC is close to that of epithelial cells with a high grade of differentiation of proximal part of renal cortex of control mammals and epithelial cells of proximal part of renal cortex of tumors with a high grade of differentiation (G1) in patients at CCRCC. Conclusions: the ultrastructure of tumoral cells with an average electronic density of tumors with a high grade of differentiation (G1) at CCRCC is a more «normalized» in comparative plan than the same epithelial cells with the average (G2) and the low (G3) grades of differentiation at CCRCC.
References
Eyden B, Banerjee SS, Ru Y, et al. The ultrastructure of human tumours: applications in diagnosis and research. Heidelberg, 2013. 680 p.
Gao Ch, D’Angelis ChA, Qin J, et al. Hyaline globules in epithelial neoplasm of kidney. NASD Med Sci 2013; 6 (1): 41–3.
Ribback S, Cigliano A, Kroeger N, et al. PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tudules of rats and men. Oncotarget 2015; 6 (15): 13036–48.
Tan X, He S, Han Y, et al. Establishment and characterization of clear cell renal cell carcinoma cell lines with different metastatic potential from chinese patients. Cancer Cell Int 2013; 13: 20.
Yu M, Wang H, Zhang J, et al. Expression of CIDE proteins in clear cell renal cell carcinoma and their prognostic significance. Mol Cell Biochem 2013; 378: 145–51.
Drabkin HA, Gemmill RM. Cholesterol and the develpoment of clear cell renal cell carcinoma. Curr Opin Pharmacol 2012; 12 (6): 742–50.
Aishima S, Fujita N, Mano Y, et al. p62+ Hyaline inclusions in intrahepatic cholangiocarcinoma associated with viral hepatitis or alcoholic liver disease. Am J Clin Pathol 2010; 134: 457–65.
Kim G, Rajasekaran SA, Thomas G, et al. Renal clear-cell carcinoma: an ultrastructural study on the junctional complex. Histol Histopathol 2005; 20: 35–44.
Федевич С, Поспішіль Ю, Кияк Ю та ін. Ультраструктура гіалінових глобул туморозного вузла при високодиференційованому (G 1) світлоклітинному раку нирки. В: Праці НТШ Мед науки, Т 41, Львів, 2015: 84–91.
Peired AJ, Sisti A, Romaqnani P. Renal cancer stem cells: characterization and targetes therapies. Stem Cells Int 2016; 2016: 12 p.
Peired AJ, Sisti A, Romaqnani P. Mesenchymal stem cellbased therapy for kidney disease: a review of clinical evidence. Stem Cells Int 2016; 2016: 22 p.
Nilsson H, Lindren D, Fosberg AM, et al. Primary clear cell renal carcinoma cells is play minimal mitochondrial respiratory to glycolytic inhidition by 3-Bromopyruvate. Cell Death Dis 2015; 6: e1585.
Xu G, Jiang Y, Xiao Y, et al. Fast clearance of lipid droplets through MAP1S-activated autophagy supresses clear cell renal cell carcinomas and promotes patients survival. Oncotarget 2016; 7 (5): 6255–65.
Moch H, Cubilla A, Humphrey P, et al. The 2016 WHO classification of tumors of the urinary system and male genital organs. Part A: Renal, penile, and testicular tumors. Eur Urol 2016; 70 (1): 93–103.
Janji B, Viry E, Moussay E, et al. The multifaceted role of autophagy in tumor evasion from immune surveillance. Oncotarget 2016; 7 (14): 17591–607.
Munoz LE, Lauber K, Schiller M, et al. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 2010; 6 (5): 280–89.
Schläfli AM, Berezowska S, Adams O, et al. Reliable LC3 and p62 autophagy marker detection in fixed paraffin embedded human tissue by immunochemistry. Eur J Histochem 2015; 59 (2481): 137–44.
Kishi-Hakura C, Koyama-Honda I, Itakura E, et al. Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells. J Cell Sci 2014; 127: 4089–102.
Зербіно ДД, Багрій ММ, Дядик ОО та ін. Судинна патологія нирок. Вінниця: Нова книга, 2015. 456 с.
Зербіно ДД, Багрій ММ, Боднар ЯЯ та ін. Патоморфологія та гістологія (атлас). Вінниця: Нова книга, 2016. 800 с.
Delahunt B, McKenney JK, Lohse CM, et al. A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis. Am J Surg Pathol 2013; 37 (3): 311–22.
Kim HK, Song KS, Park YS, et al. Elevated levels of circulating platelet microparticles. VEGF, IL-6 and RANTES in patients with gastric cancer: posible role of a metastasis predictor. Eur J Cancer 2003; 39 (2): 184–91.
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420 (6917): 860–67.
Padera TP, Stoll BR, Tooredman JB, et al. Pathology: cancer cells compress intratumour vessels. Nature 2004; 427 (6976): 695.
Denaro N, Tomasello L, Russi EG. Cancer and stress: what’s matter from epidemiologist and oncologist point of view? J Cancer Terр Res 2014; 3: 3–11.
Бережная НМ, Чехун ВФ. Физиологическая система соединительной ткани и онкогенез. І. Роль клеточных компонентов стромы в развитии опухоли. Онкология 2016; 18 (1): 6–11.
Бережная НМ, Чехун ВФ. Физиологическая система соединительной ткани и онкогенез. ІI. Экстрацеллюлярный матрикс и метастазирование. Онкология 2016; 18 (3): 164–76.
Sainz JrB, Carron E, Vallespinos M, et al. Cancer stem cells and macrophages: implications in tumor biology and therapeutic strategies. Mediators Inflam 2016; 2016: 9012369.
Farnsworth RH, Lackmann M, Achen MG, et al. Vascular remodeling in cancer. Oncogene 2014; 33 (27): 3496–505.
Li J, Kluiver J, Osinga J, et al. Functional studies of primary tubular epithelial cells indicate a tumor suppressor role of SETD2 in clear cell renal cell carcinoma. Neoplasma 2016; 18 (6): 339–46.
Lobo NC, Gedye C, Apostols AJ, et al. Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinova patients: clinically relevant models from research and personalized medicine. BMC Cancer 2016; 16: 485.
Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982; 6: 655–63.
Романенко АМ, Непомнящий ВВ, Забарко ЛБ. Епітеліальні пухлини нирки: сучасна міжнародна гістологічна класифікація. Урологія 2002; 4: 48–54.
Чердынцева ТМ, Бобров ИП, Климачев ВВ и др. Размер опухолевого узла и гистологическое строение перитуморозной зоны рака почки. Фундаментальные исследования 2013; 7: 188–93.
Glauert AM. Fixation, dehydration and embedding of biological specimens: Practical methods in electron microscopy. North-Holland: American Elsevier, 1975. 207 p.
Reynolds ES. The use of lead citrate at high pH as an electronopague stain in electron microscopy. J Cell Biology 1963; 17: 208–12.
Stempac JG, Ward RT. An improved staining method for electron microscopy. J Cell Biology 1964; 22: 697–701.
Liao L, Testa JR, Yanq H. The role of chromatin-remodelers and epigenetic modifiers in kidney cancer. Cancer Genet 2015; 208 (5): 206–14.
Gstalder C, Ader I, Cuvillier O. FTY720 (Fingolimod) inhibits HIF1 and HIF2 signaling, promotes vascular remodeling, and chemosensitzez in renal cell carcinoma animal model. Mol Cancer Ther 2016; 15 (10): 1–10.
Чехун ВФ, Шербан СД, Савцова ЗД. Гетерогенность опухоли — динамическое состояние. Онкология 2012; 14 (1): 4–12.
Pacurari M, Qian Y, Fu W, et al. Cell permeability migration, and reactive oxygen species induced by multiwalled carbon nanotubules in human microvascular endotelial cells. J Toxicol Environ Health A 2012; 75 (3): 129–47.
Williams KC, Wong E, Leong HS, et al. Cancer dissemination from a physical sciences perspective. Converd Sci Phys Oncol 2016; 2 (2): 023001.
Bezpalko L, Gavrilyuk E, Zayachkivska O. Impact of prenatal exposure to obesogenic environment on later-life brown and white adipocytes and liver outcomes. In: Proc Shevchenko Sci Soc. Medicine, Lviv, 2015; 41: 33–52.
Wloga D, Strzyzewsra-Jowko I, Gaertig J, et al. Septins stabilize mitochondria in Tetrahymena termophilia. Eucaryotic Cell 2008; 7 (8): 1373–86.
Zancanaro C, Carmielli VP, Moretti C, et al. An ultrastructural study brown adipose tissue in pre-term human new-borns. Tissue Cell 1995; 27 (3): 339–48.
Ward JM, Stevens JL, Konishi N, et al. Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans. Am J Pathol 1992; 141 (4): 955–64.
Obokata H, Wakayaama T, Sasai Y, et al. Stimulus triggerd fate convtrsion of somatic cells into pluripotency. Nature 2014; 505 (7485): 641–7.
