Lviv clinical bulletin 2016, 4(16): 27-35

https://doi.org/10.25040/lkv2016.04.027

Ultrastructural Organization of Microcirculatory Bed in Clear Cell Renal Cell Carcinoma of Different Grades of Differentiation

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S. Fedevych

Danylo Halytsky Lviv National Medical University

Introduction. Implementing into medical practice target therapy in cancer patients including the conventional (clear cell) renal cell carcinoma (CCRCC) provides the delivery of anti-angiogenic and conventional cytoreductive agents through “normalized” ways of the vascular network of tumors to cancer cells. We also know that microcirculatory bed and its microenvironment in tumors are formed by vasculogenesis and angiogenesis, unlike normal tissues, are characterized by the presence of primitive vessels and abnormal microenvironment. However, no stu dies were conducted, which would have characterized in comparative plan the ultrastructural organization of tumor microvessels in CCRCC of different grades of differentiation.

The aim is to examine ultrastructural organization of microcirculatory bed in conventional (clear cell) renal cell carcinoma of different grades of differentiation.

Materials and methods. Material for conducting transmission electron microscopic researches was postoperative biopsies of peripheral and central parts of tumors in CCRCC at high differentiated cancer (G 1) – three cases: one man (61-years-old) and two women (49- and 61-years-old); with an average grade of differentiation (G 2) – three cases: two men (43- and 66-years-old) and one woman (69-years-old); with a low grade of differentiation (G 3) – six cases, all were men (48-, 52-, 56-, 70-, 71-, 75-year-old).

Material for conducting of сontrol studies in transmission electron microscopy was postoperative biopsies of renal cortex of eliminated parts of the kidney with tumor and the whole kidney with tumor in these patients with CCRCC.

The technique is common in transmission electron microscopy.

Results and discussion. At the ultrastructural level, vascular buds, primordial endothelial cells, optimally developed capillaries, forming capillaries, already formed capillaries, small venules, primitive capillaries, hematopoietic cells, mesenchymal cells, fi  bers of collagen studied in peripheral stroma of tumors with high differentiated (G 1) CCRCC. In the central part of the tumors there are small numbers of cells that are in the process of apoptosis, decomposition and necrosis. Gaps of disorganized capillaries are rich in accumulations of erythrocytes, platelets and fi  brin monomer bundles of fi  bers, gaps of small venules with wrinkled walls are rich in a homogenous blood plasma.

The sclerotized stroma of tumors with an average grade of differentiation (G 2) CCRCC contains mesenchymal cells, disorganized bands of primordial endothelial cells, hypertrophic capillaries and small venules. The luminal surfaces of endothelial cells of the vessels are formed by a large number of microvilli. Their gaps contain hyperaggregates of erythrocytes, polymorphonuclear granulocytes, monocytes, platelets with high electron density, fibrin polymer bundles of fi  bers, the large drops of lipoprotein.

At the low grade of differentiation (G 3) CCRCC, the considerable areas of epithelium- and endothelium-containing formations of peripheral and more central parts of the tumor are disorganized, and are in a state of apoptosis and necrosis. It was observed that the modified tumor apoptotic epithelial cells with surrounding fibrin polymer bundles of fibers and adjacent the remodulated stroma were rich in mononuclear cells, monocytes, hematopoietic cells, mesenchymal cells, primordial endothelial cells, vascular buds, capillaries of sinusoidal type, primitive capillaries, newly formed capillaries and small venules.

The control studies made it possible to establish that the ultrastructural organization of optimally developed capillaries of peripheral part of tumors with high differentiated grade CCRCC is close to that of peritubular capillaries of renal cortex of patients with high differentiated (G 1) CCRCC and kidney of mammals.

Conclusions. The ultrastructure of microcirculatory bed of tumors with a high grade of differentiation (G 1) is a more “normalized” than the average one (G 2) and the low (G 3) grade of differentiation CCRCC.

References

  1. Akinfeyev V. The regularities between angiographic semiotics of renal cell carcinoma and morphological structure of the tumor. News of Beam Diagnostics. 2004;1. Aviable mode: http://nld.by/104/stat1.htm). (Russian).
  2. Alekseyev B, Shegai P. Target therapy for disseminated renal cancer. Oncourology. 2007;4:6-11. (Russian).
  3. Berezhnaya N, Chekhu V. Physiological system of conjunctive tissue and oncogenesis. I. Role of cellular components of stroma in tumor development. Oncology. 2016;18(1):4-14. (Ukrainian).
  4. Bobryk I, Shevchenko Sh, Cherkasov V. The development of blood and lymphatic vessels. Kyiv: Zdorov’ya, 1991. 208 p. (Ukrainian).
  5. Dmitruk IM. Morphogenesis of vascular bed in epithelial tumors and there metastases [dissertation]. Lviv, 1987. 18 p. (Ukrainian).
  6. Zerbino D, Dmitruk I. Morphogenesis of intratumor vascular proliferation. Arkhiv Patologii. 1983;45(4):80-83. (Russian).
  7. Zerbino D. Common regularities of ultrastructural transformation of capillaries in hypoxia. Proceedings of materials the republic conference; 1974 Sept 26-27. Lviv, 1974. p. 174-175. (Ukrainian).
  8. Konenkov VI, Konenkov VV. Vasculogenesis and angiogenesis in diabetes mellitus: novel pathogenetic concepts for treatvent of vascular complications. Diabetes mellitus. 2012;4:17-27. (Russian).
  9. Kyyak Y, Barnett O, Kovalyshyn V, Kyyak H. Correlations between clinical and cellular cardiology (clinical and ultrastructural examinations. Lviv: Quart, 2012. 160 p. (Ukrainian).
  10. Lisyaniy N. Mesenchimal stem cells and carcinogenesis. Oncology. 2013;15(1):4-8. (Ukrainian).
  11. Lugovskoi E, Makogonenko E, Komisarenko S. Molecular mechanisms of formation and degradation of fibrin. Kyiv: Nauk dumka, 2013. 231 p. (Ukrainian).
  12. Cherdantseva TM, Bobrov IP, Klimachev VV, Bryukhanov VM, Lazarev AF, Avdalyan AM et al. The size of a tumour and histologic structure peritumorous zonez of cancer of a renal cell carcinoma. Fundamental research. 2013;7:188-193. (Russian).
  13. Spirina L, Kondakova I, Usynin E, Vintizenko S. Angiogenesis regulation in renal and bladder cancers. Sibirian Journal of Oncology. 2008;4:65-70. (Russian).
  14. Zerbino D, Bagrii M, Dyadyk O et al. Vascular renal disease. Vinnycya: Nova knyha, 2015. 456 p. (Ukrainian).
  15. Shachlamov V. The capillaries (electron microscopic examination). Moskow: Medycyna, 1971. 198 p. (Russian).
  16. Shparyk Y. Kidney cancer: recent achievements of medical treatment. Oncology. 2008;10(4):436-442. (Ukrainian).
  17. Kovalychyn V, Gzegotskyi M, Fedevych S et al. Phenomenon of enantiomorphism in trombin- and plasmin-dependent coagulative and peptizative genesis of renal cortex ultrastructural homeostasis. Experimental and Clinical Physiology and Biochemistry. 2008;2:41-58. (Ukrainian).
  18. Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag. 2006;2(3):281-290. https://doi.org/10.2147/vhrm.2006.2.3.213
  19. Bancroft WD, Rutzler JE. Reversible coagulation in living tissue. II. Chemistry. 1931;17:186-192. https://doi.org/10.1073/pnas.17.4.186
  20. Bussolati B, Brossa A, Camussi G. Resident stem cells and renal carcinoma [Internet]. Int J Nefrol. 2011. Available from: http://www.hindawi.com/journals/ijn/2011/286985/.
  21. Sainz JrB, Carron E, Vallespinos M, Machado HL. Cancer stem Cells and macrophages: Implications in tumor biology and therapeutic strategies [Internet]. Mediators 2016;2016. Available from: http://dx.doi.org/10.1155/2016/9012369. https://doi.org/10.1155/2016/9012369
  22. Charleswirth PJS, Harris AL. Mechanism of disease: angiogenesis in urologic malignancies. Nature Clin. Pract. 2006;3:157-169. https://doi.org/10.1038/ncpuro0434
  23. Coussens LM. Inflammation and cancer. Nature. 2002;420(6917):860-867. https://doi.org/10.1038/nature01322
  24. Delahunt B, Eble JN. History of the development of the classification of renal cell neoplasia. Clin Lab Med. 2005;25(2):231-246. https://doi.org/10.1016/j.cll.2005.01.007
  25. Li Calzi S, Neu MB, Shaw LC, Grant MB. Endotelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits. EPMAJ. 2010;1(1):88-100. https://doi.org/10.1007/s13167-010-0011-8
  26. Glauert AM, editor. Fixation, dehydration and embedding of biological specimens: Practical methods in electron North-Hollond: American Elsevier, 1975. 207 p.
  27. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82(1):4-6. https://doi.org/10.1093/jnci/82.1.4
  28. Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6(5):655-663. https://doi.org/10.1097/00000478-198210000-00007
  29. Green D, Kwaan HC. Coagulation in cancer. New York: Springer Science. Business Media, 2009. 327 p.
  30. Liao D, Johnson RS. Hypoxia: A key regulator of angiogenesis in cancer. Cancer Metastasis Rev. 2007;26(2):281-290. https://doi.org/10.1007/s10555-007-9066-y
  31. Maunsbach FB, Christensen EI. Functional ultrastructure of the proxymal tubule. In: Renal Physiology. Windhager EE, editor. 2nd ed. New York: American Physiological Society by Oxford University Press, 1992. р. 41-107.
  32. Padera TP, Stoll BR, Tooredman JB, Capen D, di Tomaso E, Jain RK. Pathology: cancer cells compress intratumour vessels. Nature. 2004;427(6976):695. https://doi.org/10.1038/427695a
  33. Rakesh KJ. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Scince. 2005;307(5706):58-62. https://doi.org/10.1126/science.1104819
  34. Goligorsky MS, Kuo MC, Patschan D, Verhaar MC. Review article: endothelial progenitor cells in renal disease. Nephrology (Carlton). 2009;14(3):291-297. https://doi.org/10.1111/j.1440-1797.2009.01112.x
  35. Reynolds ES. The use of lead citrate at high pH as an electronopague stain in electron microscopy. J Cell Biology. 1963;17:208-212. https://doi.org/10.1083/jcb.17.1.208
  36. Rioux-Leclercq N. The Fuhrman grading system for kidney cancer prognosis. Prog. 2006;16(4 Suppl):5-8.
  37. Semenza GL. Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodeling. J Cell Biochem. 2007;102(4):109-117. https://doi.org/10.1002/jcb.21523
  38. Stempac JG, Ward RT. An improved staining method for electron microscopy. J Cell Biology. 1964;22:697-701. https://doi.org/10.1083/jcb.22.3.697
  39. Tang DG, Conti CJ. Endothelial cell development, vasculogenesis, angiogenesis, and tumor neovascularisation: an update. Semin Thromb Hemost. 2004;30(1):840-847.
  40. Verheul HM, van Erp K, Homs MY, Yoon GS, van der Groep P, Rogers C et al. The relationship of vascular endothelial growth factor and coagulation factor fibrin and fibrinogen expression in clear cell renal cell carcinoma. Urology. 2010;75(3):608-614. https://doi.org/10.1016/j.urology.2009.05.075
  41. Koesters R, Kaissling B, LeHir M, Picard N, Theilig F, Gebhardt R et al. Tubular overexpression of transforming growth factor-β1 induces autophagy and fibrosis dut not mesenchymal transition of Renal Epithelial Cells. Am J Pathol. 2010;177(2):632-634. https://doi.org/10.2353/ajpath.2010.091012
  42. Warren BA, Greenblatt M, Kommineni VRC. Tumour angiogenesis: ultrastructure of endothelial cells in mitosis. Br J Exp Path. 1972;53(2):216-224.