14-3-3σ is a protein expressed in many epithelial tissues associated with essential cell functions, including cell-cycle control, apoptosis, and cytoskeletal integrity. There is a paucity of knowledge of the tumorigenesis of canine renal cell carcinomas (RCCs), and the histological origin of this tumor has not been established. This study analyzed the expression of 14-3-3σ, Ki-67, cytokeratins, and vimentin in 40 canine RCCs. Aberrant expression of 14-3-3σ was demonstrated in 15 (38%) cases and was associated with a significantly shorter survival time (P < .002). In contrast to canine RCC, normal kidney did not express 14-3-3σ. The Ki-67 proliferation index did not show utility as a prognostic factor. The distal convoluted tubular epithelium in normal kidneys coexpressed cytokeratins and vimentin, and thus maintenance of this coexpression pattern in canine RCC suggests that most tumors arise from the distal segment of the nephron. These results suggest that 14-3-3σ is a potential negative prognostic factor and a possible therapeutic target.
AlpersCEChangA. The kidney. In: KumarVAbbasAKAsterJC, eds. Pathologic Basis of Disease, 9th ed. Philadelphia, PA: Elsevier; 2015:953–953.
2.
BabulaJJLiuJY. Integrate omics data and molecular dynamics simulations toward better understanding of human 14-3-3 interactomes and better drugs for cancer therapy. J Genet Genomics. 2015;42(10):531–547.
3.
BryanJNHenryCJTurnquistSE. Primary renal neoplasia of dogs. J Vet Intern Med. 2006;20(5):1155–1160.
4.
CalazansSGAlvesCEFZanettiNM. Metastatic kidney carcinoma causing paralysis of pelvic limbs in a dog. Pak Vet J. 2016;36(1):124–126.
5.
CarvalhoSStollALPriestnallSL. Retrospective evaluation of COX-2 expression, histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy [published online August 31, 2016]. Vet Comp Oncol.
6.
ChanTAHermekingHLengauerC. 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature. 1999;401(6753):616–620.
7.
ChenLYangB. 14-3-3 sigma is a useful immunohistochemical marker for diagnosing ovarian granulosa cell tumors and steroid cell tumors. Int J Gynecol Pathol. 2013;32(2):156–162.
8.
CiancioloREMohrFE. Urinary system. In: MaxieMG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. St Louis, MO: Elsevier; 2015:444–446.
9.
EdmondsonEFHessAMPowersBE. Prognostic significance of histologic features in canine renal cell carcinomas: 70 nephrectomies. Vet Pathol. 2015;52(2):260–268.
10.
GarimellaPSSarnakMJ. Uromodulin in kidney health and disease. Curr Opin Nephrol Hypertens. 2017;26(2):136–142.
11.
GayedBAYoussefRFBagrodiaA. Ki67 is an independent predictor of oncological outcomes in patients with localized clear-cell renal cell carcinoma. BJU Int. 2014;113(4):668–673.
12.
Gil da CostaRMOliveiraJPSaraivaAL. Immunohistochemical characterization of 13 canine renal cell carcinomas. Vet Pathol. 2011;48(2):427–432.
13.
HermekingH. The 14-3-3 cancer connection. Nat Rev Cancer. 2003;3(12):931–943.
14.
HermekingHLengauerCPolyakK. 14-3-3sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell. 1997;1(1):3–11.
15.
KelleyLCCrowellWAPuetteM. A retrospective study of multicentric bovine renal cell tumors. Vet Pathol. 1996;33(2):133–141.
16.
KoSKimJYJeongJ. The role and regulatory mechanism of 14-3-3 sigma in human breast cancer. J Breast Cancer. 2014;17(3):207–218.
17.
LiZLiuJYZhangJT. 14-3-3sigma, the double-edged sword of human cancers. Am J Transl Res. 2009;1(4):326–340.
18.
LodyginDHermekingH. Epigenetic silencing of 14-3-3sigma in cancer. Semin Cancer Biol. 2006;16(3):214–224.
19.
MeutenDJEverittJInskeepW. Histological Classification of Tumors of the Urinary System of Domestic Animals. Vol 11. Washington, DC: Armed Forces Institute of Pathology; 2004.
20.
MeutenDJMeutenTLK. Tumors of the urinary system. In: MeutenDJ, ed. Tumors in Domestic Animals, 5th ed. Ames, IA: Wiley Blackwell; 2017:632–688.
21.
MeutenDJMooreFMGeorgeJW. Mitotic count and the field of view area: time to standardize. Vet Pathol. 2016;53(1):7–9.
22.
MhawechPBenzACeratoC. Downregulation of 14-3-3sigma in ovary, prostate and endometrial carcinomas is associated with CpG island methylation. Mod Pathol. 2005;18(3):340–348.
23.
MikamiTMaruyamaSAbeT. Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration. Virchows Arch. 2015;466(5):559–569.
24.
NakajimaTShimookaHWeixaP. Immunohistochemical demonstration of 14-3-3 sigma protein in normal human tissues and lung cancers, and the preponderance of its strong expression in epithelial cells of squamous cell lineage. Pathol Int. 2003;53(6):353–360.
25.
NgoTCWoodCGKaramJA. Biomarkers of renal cell carcinoma. Urol Oncol. 2014;32(3):243–251.
26.
OlumiAFWeidnerNPrestiJC. p53 immunoreactivity correlates with Ki-67 and bcl-2 expression in renal cell carcinoma. Urol Oncol. 2001;6(2):63–67.
27.
Ramos-VaraJAKiupelMBaszlerT; American Association of Veterinary Laboratory Diagnosticians Subcommittee on Standardization of Immunohistochemistry. Suggested guidelines for immunohistochemical techniques in veterinary diagnostic laboratories. J Vet Diagn Invest. 2008;20(4):393–413.
28.
SchufflerPJFuchsTJOngCS. A free software toolkit for histopathological cell counting and staining estimation. J Pathol Inform. 2013;4(suppl):S2.
29.
ShenJRiggsPKHensleySC. Differential expression of multiple anti-apoptotic proteins in epidermis of IGF-1 transgenic mice as revealed by 2-dimensional gel electrophoresis/mass spectrometry analysis. Mol Carcinog. 2007;46(5):331–340.
30.
ShenSSTruongLDScarpelliM. Role of immunohistochemistry in diagnosing renal neoplasms: when is it really useful?Arch Pathol Lab Med. 2012;136(4):410–417.
31.
Shiba-IshiiAKanoJMorishitaY. High expression of stratifin is a universal abnormality during the course of malignant progression of early-stage lung adenocarcinoma. Int J Cancer. 2011;129(10):2445–2453.
32.
Shiba-IshiiAKimYShiozawaT. Stratifin accelerates progression of lung adenocarcinoma at an early stage. Mol Cancer. 2015;14:142.
33.
Suárez-BonnetAde las MulasJMHerraezP. Immunohistochemical localisation of 14-3-3 sigma protein in normal canine tissues. Vet J. 2010;185(2):218–221.
34.
Suárez-BonnetAHerraezPMartin de lasMulas J. Expression of 14-3-3 sigma protein in normal and neoplastic canine mammary gland. Vet J. 2011;190(3):345–351.
35.
Suárez-BonnetAHerraezPAguirreM. Expression of cell cycle regulators, 14-3-3sigma and p53 proteins, and vimentin in canine transitional cell carcinoma of the urinary bladder. Urol Oncol. 2015;33(7):332.e1–e7.
36.
Suárez-BonnetAAguirre-SanceledonioMAndradaM. Comparison of immunoreaction between two commercial antibodies against 14-3-3σ protein in canine tissues. J Appl Anim Res. 2016;44(1):83–86.
WuYJJanYJKoBS. Involvement of 14-3-3 proteins in regulating tumor progression of hepatocellular carcinoma. Cancers (Basel). 2015;7(2):1022–1036.
39.
ZhangYLiYLinC. Aberrant upregulation of 14-3-3sigma and EZH2 expression serves as an inferior prognostic biomarker for hepatocellular carcinoma. PLoS One. 2014;9(9):e107251.
40.
ZhaoJMeyerkordCLDuY. 14-3-3 proteins as potential therapeutic targets. Semin Cell Dev Biol. 2011;22(7):705–712.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
