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Genitourinary Neoplasms

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Practical Oncologic Molecular Pathology

Part of the book series: Practical Anatomic Pathology ((PAP))

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Abstract

Genitourinary neoplasms are biologically diverse, and molecular testing is showing an emerging role in clinical practice, including diagnosis, prognosis, and risk-stratification of treatment. This chapter provides a practical overview of the frequently used molecular tests available for genitourinary neoplasms which include tumors of kidney, bladder, prostate, and testis. Representative case studies are presented to highlight practical indications and utilization of molecular diagnostic tests. The chapter contains 14 questions and 3 case presentations; each question and case are addressed with a table, concise note, and representative pictures if applicable. Some newly described prognostic biomarkers, such as PTEN and diagnostic tests, such as gene expression profiling, are included. Some of these markers are still under investigation to further prove clinical applications.

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References

  1. Brugarolas J. Molecular genetics of clear-cell renal cell carcinoma. J Clin Oncol. 2014;32(18):1968–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Magers MJ, Cheng L. Practical molecular testing in a clinical genitourinary service. Arch Pathol Lab Med. 2020;144(3):277–89.

    Article  CAS  PubMed  Google Scholar 

  3. Klatte T, Said JW, Seligson DB, Rao PN, de Martino M, Shuch B, et al. Pathological, immunohistochemical and cytogenetic features of papillary renal cell carcinoma with clear cell features. J Urol. 2011;185(1):30–5.

    Article  PubMed  Google Scholar 

  4. Chen YB, Xu J, Skanderup AJ, Dong Y, Brannon AR, Wang L, et al. Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets. Nat Commun. 2016;7:13131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Piva F, Santoni M, Matrana MR, Satti S, Giulietti M, Occhipinti G, et al. BAP1, PBRM1 and SETD2 in clear-cell renal cell carcinoma: molecular diagnostics and possible targets for personalized therapies. Expert Rev Mol Diagn. 2015;15(9):1201–10.

    Article  CAS  PubMed  Google Scholar 

  6. Speicher MR, Schoell B, du Manoir S, Schrock E, Ried T, Cremer T, et al. Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am J Pathol. 1994;145(2):356–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26(3):319–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Delongchamps NB, Galmiche L, Eiss D, Rouach Y, Vogt B, Timsit MO, et al. Hybrid tumour ‘oncocytoma-chromophobe renal cell carcinoma’ of the kidney: a report of seven sporadic cases. BJU Int. 2009;103(10):1381–4.

    Article  PubMed  Google Scholar 

  9. Petersson F, Gatalica Z, Grossmann P, Perez Montiel MD, Alvarado Cabrero I, Bulimbasic S, et al. Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases. Virchows Arch. 2010;456(4):355–65.

    Article  PubMed  Google Scholar 

  10. Pitra T, Pivovarcikova K, Alaghehbandan R, Hes O. Chromosomal numerical aberration pattern in papillary renal cell carcinoma: review article. Ann Diagn Pathol. 2019;40:189–99.

    Article  PubMed  Google Scholar 

  11. Saleeb RM, Brimo F, Farag M, Rompre-Brodeur A, Rotondo F, Beharry V, et al. Toward biological subtyping of papillary renal cell carcinoma with clinical implications through histologic, immunohistochemical, and molecular analysis. Am J Surg Pathol. 2017;41(12):1618–29.

    Article  PubMed  Google Scholar 

  12. Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 1997;16(1):68–73.

    Article  CAS  PubMed  Google Scholar 

  13. Zbar B, Tory K, Merino M, Schmidt L, Glenn G, Choyke P, et al. Hereditary papillary renal cell carcinoma. J Urol. 1994;151(3):561–6.

    Article  CAS  PubMed  Google Scholar 

  14. Dharmawardana PG, Giubellino A, Bottaro DP. Hereditary papillary renal carcinoma type I. Curr Mol Med. 2004;4(8):855–68.

    Article  CAS  PubMed  Google Scholar 

  15. Rhoades Smith KE, Bilen MA. A review of papillary renal cell carcinoma and MET inhibitors. Kidney Cancer. 2019;3(3):151–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gilbert JA. Savolitinib for MET-driven papillary renal cell carcinoma. Lancet Oncol. 2017;18(8):e440.

    Article  PubMed  Google Scholar 

  17. Akhtar M, Al-Bozom IA, Al HT. Papillary Renal Cell Carcinoma (PRCC): an update. Adv Anat Pathol. 2019;26(2):124–32.

    Article  PubMed  Google Scholar 

  18. Lubensky IA, Schmidt L, Zhuang Z, Weirich G, Pack S, Zambrano N, et al. Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype. Am J Pathol. 1999;155(2):517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Argani P. MiT family translocation renal cell carcinoma. Semin Diagn Pathol. 2015;32(2):103–13.

    Article  PubMed  Google Scholar 

  20. Green WM, Yonescu R, Morsberger L, Morris K, Netto GJ, Epstein JI, et al. Utilization of a TFE3 break-apart FISH assay in a renal tumor consultation service. Am J Surg Pathol. 2013;37(8):1150–63.

    Article  PubMed  Google Scholar 

  21. Rao Q, Williamson SR, Zhang S, Eble JN, Grignon DJ, Wang M, et al. TFE3 break-apart FISH has a higher sensitivity for Xp11.2 translocation-associated renal cell carcinoma compared with TFE3 or cathepsin K immunohistochemical staining alone: expanding the morphologic spectrum. Am J Surg Pathol. 2013;37(6):804–15.

    Article  PubMed  Google Scholar 

  22. Harrison WJ, Andrici J, Maclean F, Madadi-Ghahan R, Farzin M, Sioson L, et al. Fumarate hydratase-deficient uterine leiomyomas occur in both the syndromic and sporadic settings. Am J Surg Pathol. 2016;40(5):599–607.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Trpkov K, Hes O, Agaimy A, Bonert M, Martinek P, Magi-Galluzzi C, et al. Fumarate hydratase-deficient renal cell carcinoma is strongly correlated with fumarate hydratase mutation and hereditary leiomyomatosis and renal cell carcinoma syndrome. Am J Surg Pathol. 2016;40(7):865–75.

    Article  PubMed  Google Scholar 

  24. Gill AJ. Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia. Pathology. 2012;44(4):285–92.

    Article  CAS  PubMed  Google Scholar 

  25. Gill AJ. Succinate dehydrogenase (SDH)-deficient neoplasia. Histopathology. 2018;72(1):106–16.

    Article  PubMed  Google Scholar 

  26. Cheng L, Williamson SR, Zhang S, Maclennan GT, Montironi R, Lopez-Beltran A. Understanding the molecular genetics of renal cell neoplasia: implications for diagnosis, prognosis and therapy. Expert Rev Anticancer Ther. 2010;10(6):843–64.

    Article  CAS  PubMed  Google Scholar 

  27. Huppmann AR. Educational case: Wilms tumor. Acad Pathol. 2018;5:2374289518781582.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Halling KC, Kipp BR. Bladder cancer detection using FISH (UroVysion assay). Adv Anat Pathol. 2008;15(5):279–86.

    Article  CAS  PubMed  Google Scholar 

  29. Moonen PM, Merkx GF, Peelen P, Karthaus HF, Smeets DF, Witjes JA. UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer. Eur Urol. 2007;51(5):1275–80. discussion 80

    Article  PubMed  Google Scholar 

  30. Dimashkieh H, Wolff DJ, Smith TM, Houser PM, Nietert PJ, Yang J. Evaluation of urovysion and cytology for bladder cancer detection: a study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol. 2013;121(10):591–7.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Giedl J, Rogler A, Wild A, Riener MO, Filbeck T, Burger M, et al. TERT core promotor mutations in early-onset bladder cancer. J Cancer. 2016;7(8):915–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rachakonda PS, Hosen I, de Verdier PJ, Fallah M, Heidenreich B, Ryk C, et al. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc Natl Acad Sci U S A. 2013;110(43):17426–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhong M, Tian W, Zhuge J, Zheng X, Huang T, Cai D, et al. Distinguishing nested variants of urothelial carcinoma from benign mimickers by TERT promoter mutation. Am J Surg Pathol. 2015;39(1):127–31.

    Article  PubMed  Google Scholar 

  34. Wang CC, Huang CY, Jhuang YL, Chen CC, Jeng YM. Biological significance of TERT promoter mutation in papillary urothelial neoplasm of low malignant potential. Histopathology. 2018;72(5):795–803.

    Article  PubMed  Google Scholar 

  35. Isharwal S, Hu W, Sarungbam J, Chen YB, Gopalan A, Fine SW, et al. Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder. J Pathol. 2019;248(3):260–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Kurtis B, Zhuge J, Ojaimi C, Ye F, Cai D, Zhang D, et al. Recurrent TERT promoter mutations in urothelial carcinoma and potential clinical applications. Ann Diagn Pathol. 2016;21:7–11.

    Article  PubMed  Google Scholar 

  37. Cheng L, Davidson DD, Wang M, Lopez-Beltran A, Montironi R, Wang L, et al. Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change. Histopathology. 2016;69(1):107–13.

    Article  PubMed  Google Scholar 

  38. Sjodahl G, Lauss M, Lovgren K, Chebil G, Gudjonsson S, Veerla S, et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res. 2012;18(12):3377–86.

    Article  CAS  Google Scholar 

  39. Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171(3):540–56. e25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bohlander SK. ETV6: a versatile player in leukemogenesis. Semin Cancer Biol. 2005;15(3):162–74.

    Article  CAS  PubMed  Google Scholar 

  41. Khoury JD. Ewing sarcoma family of tumors. Adv Anat Pathol. 2005;12(4):212–20.

    Article  PubMed  Google Scholar 

  42. Hollenhorst PC, McIntosh LP, Graves BJ. Genomic and biochemical insights into the specificity of ETS transcription factors. Annu Rev Biochem. 2011;80:437–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kumar-Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 2008;8(7):497–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644–8.

    Article  CAS  PubMed  Google Scholar 

  45. Jamaspishvili T, Berman DM, Ross AE, Scher HI, De Marzo AM, Squire JA, et al. Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. 2018;15(4):222–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lotan TL, Wei W, Ludkovski O, Morais CL, Guedes LB, Jamaspishvili T, et al. Analytic validation of a clinical-grade PTEN immunohistochemistry assay in prostate cancer by comparison with PTEN FISH. Mod Pathol. 2016;29(8):904–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Picanco-Albuquerque CG, Morais CL, Carvalho FL, Peskoe SB, Hicks JL, Ludkovski O, et al. In prostate cancer needle biopsies, detections of PTEN loss by fluorescence in situ hybridization (FISH) and by immunohistochemistry (IHC) are concordant and show consistent association with upgrading. Virchows Arch. 2016;468(5):607–17.

    Article  CAS  PubMed  Google Scholar 

  48. Lotan TL, Heumann A, Rico SD, Hicks J, Lecksell K, Koop C, et al. PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort. Oncotarget. 2017;8(39):65566–76.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bismar TA, Hegazy S, Feng Z, Yu D, Donnelly B, Palanisamy N, et al. Clinical utility of assessing PTEN and ERG protein expression in prostate cancer patients: a proposed method for risk stratification. J Cancer Res Clin Oncol. 2018;144(11):2117–25.

    Article  CAS  PubMed  Google Scholar 

  50. Reid AH, Attard G, Ambroisine L, Fisher G, Kovacs G, Brewer D, et al. Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer. 2010;102(4):678–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lotan TL, Gurel B, Sutcliffe S, Esopi D, Liu W, Xu J, et al. PTEN protein loss by immunostaining: analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin Cancer Res. 2011;17(20):6563–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cuzick J, Berney DM, Fisher G, Mesher D, Moller H, Reid JE, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012;106(6):1095–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Klein EA, Cooperberg MR, Magi-Galluzzi C, Simko JP, Falzarano SM, Maddala T, et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol. 2014;66(3):550–60.

    Article  PubMed  Google Scholar 

  54. Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One. 2013;8(6):e66855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kornberg Z, Cooperberg MR, Cowan JE, Chan JM, Shinohara K, Simko JP, et al. A 17-gene genomic prostate score as a predictor of adverse pathology in men on active surveillance. J Urol. 2019;202(4):702–9.

    Article  PubMed  Google Scholar 

  56. Freedland SJ, Gerber L, Reid J, Welbourn W, Tikishvili E, Park J, et al. Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86(5):848–53.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ross AE, Johnson MH, Yousefi K, Davicioni E, Netto GJ, Marchionni L, et al. Tissue-based genomics augments post-prostatectomy risk stratification in a natural history cohort of intermediate- and high-risk men. Eur Urol. 2016;69(1):157–65.

    Article  PubMed  Google Scholar 

  58. Al-Obaidy KI, Chovanec M, Cheng L. Molecular characteristics of testicular germ cell tumors: pathogenesis and mechanisms of therapy resistance. Expert Rev Anticancer Ther. 2020;20(2):75–9.

    Article  CAS  PubMed  Google Scholar 

  59. McIntyre A, Summersgill B, Grygalewicz B, Gillis AJ, Stoop J, van Gurp RJ, et al. Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults. Cancer Res. 2005;65(18):8085–9.

    Article  CAS  PubMed  Google Scholar 

  60. Kemmer K, Corless CL, Fletcher JA, McGreevey L, Haley A, Griffith D, et al. KIT mutations are common in testicular seminomas. Am J Pathol. 2004;164(1):305–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Litchfield K, Summersgill B, Yost S, Sultana R, Labreche K, Dudakia D, et al. Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours. Nat Commun. 2015;6:5973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cheng L, Lyu B, Roth LM. Perspectives on testicular germ cell neoplasms. Hum Pathol. 2017;59:10–25.

    Article  CAS  PubMed  Google Scholar 

  63. Al-Obaidy KI, Eble JN, Cheng L, Williamson SR, Sakr WA, Gupta N, et al. Papillary renal neoplasm with reverse polarity: a morphologic, immunohistochemical, and molecular study. Am J Surg Pathol. 2019;43(8):1099–111.

    Article  PubMed  Google Scholar 

  64. Al-Obaidy KI, Eble JN, Nassiri M, Cheng L, Eldomery MK, Williamson SR, et al. Recurrent KRAS mutations in papillary renal neoplasm with reverse polarity. Mod Pathol. 2020;33(6):1157–64.

    Article  CAS  PubMed  Google Scholar 

  65. Waterhouse RL Jr, Van Neste L, Moses KA, Barnswell C, Silberstein JL, Jalkut M, et al. Evaluation of an epigenetic assay for predicting repeat prostate biopsy outcome in African American men. Urology. 2019;128:62–5.

    Article  PubMed  Google Scholar 

  66. Van Neste L, Groskopf J, Grizzle WE, Adams GW, DeGuenther MS, Kolettis PN, et al. Epigenetic risk score improves prostate cancer risk assessment. Prostate. 2017;77(12):1259–64.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Laboratory Medicine, Geisinger Health, Danville, PA, USA

    Yi Ding

  2. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Khaleel I. Al-Obaidy & Liang Cheng

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  1. Yi Ding
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  3. Liang Cheng
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  1. Department of Laboratory Medicine, Geisinger Health, Danville, PA, USA

    Yi Ding

  2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Linsheng Zhang

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Ding, Y., Al-Obaidy, K.I., Cheng, L. (2021). Genitourinary Neoplasms. In: Ding, Y., Zhang, L. (eds) Practical Oncologic Molecular Pathology. Practical Anatomic Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-73227-1_11

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  • DOI: https://doi.org/10.1007/978-3-030-73227-1_11

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