Page 675 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition
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CHAPTER 30  Tumors of the Urinary System  653


           respectively. 106  The MST appears shorter for clear cell (87 days)   of the BRAF V600E  mutation that drives 8% of all human can-
           versus chromophobe, papillary, and multilocular cystic RCCs. 106    cer. Although BRAF mutations are rare in human iUC, other
                                                                 molecular variants are present that turn on the MAPK pathway
           Fuhrman nuclear grade, a human RCC histologic grading scheme
  VetBooks.ir  based on morphologic features of nuclei and nucleoli, was prog-  in approximately 30% of human iUC cases. 133  Mutations in
                                                                 several other genes implicated in the development and progres-
           nostic in one study of 70 dogs with RCC with MSTs not reached,
           1065 days, 379 days, and 87 days in dogs with grade 1, 2, 3,   sion of iUC and other cancers in humans have been identified
           and 4 RCCs, respectively. 106  Radiographic evidence of metastasis   in canine iUC including EGFR, CDKN2B, PIK 3CA, BRCA2,
           is present in 16% to 34% of dogs with primary renal tumors. 94,97    NFκB, ARHGEF4, XPA, NCOA4, MDC1, UBR5, RB1CC1,
           Metastasis at death was reported in 88% of dogs with sarcomas,   RPS6, CIITA, MITF, and  WT1. 17,128,133  Another intriguing
                                                      94
           75% with nephroblastomas, and 69% with carcinomas.    finding in canine iUC is the presence of molecular subtypes
                                                                 defined by gene signatures including luminal and basal sub-
           Feline Renal Tumors                                   types initially observed in human breast cancer and then found
                                                                 in human iUC. 127,134  This is important because cancer behav-
           Primary renal tumors are rare in the cat. Excluding lymphoma,   ior, treatment response, and prognosis differ between subtypes
           reported feline primary renal tumors include tubular RCC, tubu-  in humans. 134  
           lopapillary RCC, sarcomatoid RCC, adenocarcinoma, adenoma,
           iUC, squamous cell carcinoma, leiomyosarcoma, nephroblas-  Renal Cancer
           toma, and hemangiosarcoma. 108–115  The tubular and tubulopapil-
           lary RCC were most common in a series of 19 cats. 108  The most   Major types of renal cancer in humans include RCC, urothe-
           common presenting complaint was weight loss. Metastasis  was   lial carcinoma of the renal pelvis, and Wilms’ tumor (nephro-
           frequently detected at the time of diagnosis. 108     blastoma), which is most commonly diagnosed in children. 135
             Polycythemia  has  been reported  in cats  with  primary  renal   Renal cancer is newly diagnosed in 64,000 people and results in
           tumors. 108,115   In  two  cats  with  renal  adenocarcinoma,  polycy-  15,000 deaths each year in the United States. RCC accounts for
           themia resolved after nephrectomy. 115  Hypertrophic osteopathy   90% of adult renal carcinomas. 135  Risk factors for RCC include
           has been reported in a cat with renal adenoma. 110  In contrast to   cigarette smoking, obesity, and hypertension. 136  Multiple sub-
           canine and human RCC, immunohistochemistry did not corre-  types of RCC exist including clear cell, papillary types I and II,
           late with RCC subtype in a small series of cats. 114  Nephrectomy   and chromophobe types. The clear cell type can be sporadic or
           could be considered in unilateral cancer. The role of chemotherapy   associated with von Hippel–Lindau disease in which mutations
           is undefined. Limited information on survival is present, but most   occur in the VHL gene. With recent progress in targeted and
           reports are associated with short survival times.     immunotherapies, the outlook for human RCC has improved
                                                                 substantially in recent years.
           Comparative Aspects
                                                                 References
           Invasive Urothelial Carcinoma

           There are more than 65,000 new cases and more than 16,000     1.   Fulkerson CM, Knapp DW: Management of transitional cell carci-
           deaths from urinary bladder cancer in the United States each year,   noma of the urinary bladder in dogs: a review, Vet J 205:217–225,
           with most deaths from iUC. 116  Cigarette smoking is by far the most   2015.
           common cause of human bladder cancer. 116  In humans, more than     2.   Fulkerson CM, Dhawan D, Ratliff TL, et al.: Naturally occurring
                                                                     canine invasive urinary bladder cancer: a complementary animal
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           urethral resection and intravesical therapy, although recurrence is     3.   Knapp DW, Ramos-Vara JA, Moore GE, et al.: Urinary bladder
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           carcinoma at the time of diagnosis. Metastasis to the regional lymph     4.   Shrader S, Lauridson J, King Z, et al.: Urachal adenocarcinoma in
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           human iUC cases. 116  iUC in dogs is very similar to iUC in humans     5.   Gelberg HB: Urinary bladder mass in a dog, Vet Pathol 47:181–
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           for human invasive bladder cancer.  Successful therapies in dogs   Schweiz Arch Tierheilkd 150:565–569, 2008.
                                     2,3
           have been translated into human clinical trials, and similar effects     7.   Bae I-H, Kim Y, Pakhrin B, et al.: Genitourinary rhabdomyosar-
           observed between the two species. 2,3,126                 coma with systemic metastasis in a young dog, Vet Pathol 44:518–
             Molecular analyses have further strengthened the role of   520, 2007.
           canine TCC as a model for human iUC. 127–134  In microarray     8.   Mineshige T, Kawarai S, Yauchi T, et al.: Cutaneous epitheliotro-
           and RNA-seq analyses, hundreds of genes that are differentially   pic T-cell lymphoma with systemic dissemination in a dog, J Vet
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           found that are shared between dogs and humans. 127,128  Altered     9.   Owen  LN:  TNM classification of tumours in domestic animals,
                                                                     Geneva, 1980, World Health Organization.
           expression of genes shared between canine and human iUC    10.   Charney  VA,  Miller  MA,  Heng HG,  et  al.: Skeletal  metastasis
           includes  COX-2,  EGFR,  HER2,  p53 family genes,  DNMT1,   of canine urothelial carcinoma: pathologic and computed tomo-
           and  VIM. 121–125,129–133  The  BRAF  V595E  mutation, which is   graphic features, Vet Pathol 54:380–386, 2017.
           present in 80% of canine iUC, leads to continuous activation    11.   Reed LT, Knapp DW, Miller MA: Cutaneous metastasis of transi-
                             17
           of the MAPK pathway.  This mutation is the canine homolog   tional cell carcinoma in 12 dogs, Vet Pathol 50:676–681, 2013.
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