Kidney in VHL disease: Early clear cell proliferation occurs in the distal tubular system

A-Gharaibeh,Nayef S.; Temm,Constance J.; Shively,Sharon B.; Vortmeyer,Alexander O.

doi:10.3892/or.2022.8437

Kidney in VHL disease: Early clear cell proliferation occurs in the distal tubular system

Authors:
- Nayef S. A-Gharaibeh
- Constance J. Temm
- Sharon B. Shively
- Alexander O. Vortmeyer
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Affiliations: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
Published online on: November 1, 2022 https://doi.org/10.3892/or.2022.8437
Article Number: 222
Copyright: © A-Gharaibeh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal clear cell carcinoma commonly occurs in patients with von Hippel‑Lindau disease (VHL). Kidneys of VHL disease patients (VHL kidneys) contain an abundance of independent clear cell proliferation events that have been hypothesized to represent precursor structures of clear cell carcinoma. In the present study, it was tried to identify the site of origin of clear cell proliferation, and the immunophenotype of clear cells. Using 3D histological tracking, the topographic origin of microscopic clear cell proliferation was investigated by identification of informative structures of interest and immunohistochemical staining for cluster of differentiation 10 (CD10) and cytokeratin 7 (CK7) in consecutive serial sections. In addition, the CD10/CK7 immunophenotype of proliferating clear cells was evaluated. Clear cell proliferation uniformly occurred in the distal tubular system. Some clear cell proliferation, however, revealed proximal tubule immunophenotype. It was concluded that early proliferation of VHL‑deficient clear cells occurs in the distal tubular system. Despite the association with the distal tubular system, the immunohistochemical profile of early clear cell proliferation may be inconsistent with its distal tubular origin.

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1	Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM and Oldfield EH: Von Hippel-Lindau disease. Lancet. 361:2059–2067. 2003. View Article : Google Scholar : PubMed/NCBI
2	Glasker S, Vergauwen E, Koch CA, Kutikov A and Vortmeyer AO: Von Hippel-Lindau disease: Current challenges and future propects. Onco Targets Ther. 13:5669–5690. 2020. View Article : Google Scholar : PubMed/NCBI
3	Braunstein H and Adelman JU: Histochemical study of the enzymatic activity of human neoplasms. II. Histogenesis of renal cell carcinoma. Cancer. 19:935–938. 1966. View Article : Google Scholar : PubMed/NCBI
4	Holthöfer H, Miettinen A, Paasivuo R, Lehto VP, Linder E, Alfthan O and Virtanen I: Cellular origin and differentiation of renal carcinomas. A fluorescence microscopic study with kidney-specific antibodies, antiintermediate filament antibodies, and lectins. Lab Invest. 49:317–326. 1983.PubMed/NCBI
5	Wallace AC and Nairn RC: Renal tubular antigens in kidney tumors. Cancer. 29:977–981. 1972. View Article : Google Scholar : PubMed/NCBI
6	Gröne HJ, Weber K, Helmchen U and Osborn M: Villin-a marker of brush border differentiation and cellular origin in human renal cell carcinoma. Am J Pathol. 124:294–302. 1986.PubMed/NCBI
7	Kageyama Y, Sasaki S, Yamamura Y, Oshima H and Ikawa Y: Water channel protein subtype suggests the origin of renal cell carcinoma. J Urol. 156:291–295. 1996. View Article : Google Scholar : PubMed/NCBI
8	Motzer RJ, Bander NH and Nanus DM: Renal-cell carcinoma. N Engl J Med. 335:865–875. 1996. View Article : Google Scholar : PubMed/NCBI
9	Aizawa S, Kikuchi Y, Suzuki M and Furusato M: Renal cell carcinoma of lower nephron origin. Acta Pathol Jpn. 37:567–574. 1987.PubMed/NCBI
10	Cao Y, Karsten U, Zerban H and Bannasch P: Expression of MUC1, Thomsen-Friedenreich-related antigens, and cytokeratin 19 in human renal cell carcinomas and tubular clear cell lesions. Virchows Arch. 436:119–126. 2000. View Article : Google Scholar : PubMed/NCBI
11	Nogueira E, Klimek F, Weber E and Bannasch P: Collecting duct origin of rat renal clear cell tumors. Virchows Arch B Cell Pathol Incl Mol Pathol. 57:275–283. 1989. View Article : Google Scholar : PubMed/NCBI
12	Cohen C, McCue PA and Derose PB: Histogenesis of renal cell carcinoma and renal oncocytoma. An immunohistochemical study. Cancer. 62:1946–1951. 1988. View Article : Google Scholar : PubMed/NCBI
13	Droz D, Zachar D, Charbit L, Gogusev J, Chrétein Y and Iris L: Expression of the human nephron differentiation molecules in renal cell carcinomas. Am J Pathol. 137:895–905. 1990.PubMed/NCBI
14	Markovic-Lipkovski J, Brasanac D, Todorovic V, Müller CA and Müller GA: Immunomorphological characteristics of renal cell carcinoma. Histol Histopathol. 10:651–659. 1995.PubMed/NCBI
15	Mandriota SJ, Turner KJ, Davies DR, Murray PG, Morgan NV, Sowter HM, Wykoff CC, Maher ER, Harris AL, Ratcliffe PJ and Maxwell PH: HIF activation identifies early lesions in VHL kidneys: Evidence for site-specific tumor suppressor function in the nephron. Cancer Cell. 1:459–468. 2002. View Article : Google Scholar : PubMed/NCBI
16	Bobulescu IA, Pop LM, Mani C, Turner K, Rivera C, Khatoon S, Kairamkonda S, Hannan R and Palle K: Renal lipid metabolism abnormalities in obesity and clear cell renal cell carcinoma. Metabolites. 11:6082021. View Article : Google Scholar : PubMed/NCBI
17	Frew IJ and Moch H: A clearer view of the molecular complexity of clear cell renal cell carcinoma. Annu Rev Pathol. 10:263–289. 2015. View Article : Google Scholar : PubMed/NCBI
18	Turajlic S, Larkin J and Swanton C: SnapShot: Renal cell carcinoma. Cell. 163:1556. e12015. View Article : Google Scholar : PubMed/NCBI
19	Büttner F, Winter S, Rausch S, Reustle A, Kruck S, Junker K, Stenzl A, Agaimy A, Hartmann A, Bedke J, et al: Survival prediction of clear cell renal cell carcinoma based on gene expression similarity to the proximal tubule of the nephron. Eur Urol. 68:1016–1020. 2015. View Article : Google Scholar : PubMed/NCBI
20	Sangoi AR, Karamchandani J, Kim J, Pai RK and McKenney JK: The use of immunohistochemistry in the diagnosis of metastatic clear cell renal cell carcinoma: A review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10. Adv Anat Pathol. 17:377–393. 2010. View Article : Google Scholar : PubMed/NCBI
21	Mubarak M, Al-Gharaibeh N, Sommaruga S, Li J and Vortmeyer AO: Histological tracking into the third dimension: Evolution of early tumorigenesis in VHL kidney. J Kidney Cancer VHL. 8:5–14. 2021. View Article : Google Scholar : PubMed/NCBI
22	Schietke RE, Hackenbeck T, Tran M, Günther R, Klanke B, Warnecke CL, Knaup KX, Shukla D, Rosenberger C, Koesters R, et al: Renal tubular HIF-2α expression requires VHL inactivation and causes fibrosis and cysts. PLoS One. 7:e310342012. View Article : Google Scholar : PubMed/NCBI
23	Holm-Nielsen P and Pallesen G: Expression of segment-specific antigens in the human nephron and in renal epithelial tumors. APMIS Suppl. 4:48–55. 1988.PubMed/NCBI
24	Skinnider BF, Folpe AL, Hennigar RA, Lim SD, Cohen C, Tamboli P, Young A, de Peralta-Venturina M and Amin MB: Distribution of cytokeratins and vimentin in adult renal neoplasms and normal renal tissue: Potential utility of a cytokeratin antibody panel in the differential diagnosis of renal tumors. Am J Surg Pathol. 29:747–754. 2005. View Article : Google Scholar : PubMed/NCBI
25	Wilkerson ML, Lin F, Liu H and Cheng L: The application of immunohistochemical biomarkers in urologic surgical pathology. Arch Pathol Lab Med. 138:1643–1665. 2014. View Article : Google Scholar : PubMed/NCBI
26	van der Horst-Schrivers ANA, Sluiter WJ, Kruizinga RC, van Leeuwaarde RS, Giles R, Olderode-Berends MJW and Links TP: The incidence of consecutive manifestations in von Hippel-Lindau disease. Fam Cancer. 18:369–376. 2019. View Article : Google Scholar : PubMed/NCBI
27	Solomon D and Schwartz A: Renal pathology in von Hippel-Lindau disease. Hum Pathol. 19:1072–1079. 1988. View Article : Google Scholar : PubMed/NCBI