βIII-tubulin overexpression is linked to aggressive tumor features and shortened survival in clear cell renal cell carcinoma.

Publisher: Springer International Country of Publication: Germany NLM ID: 8307716 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1433-8726 (Electronic) Linking ISSN: 07244983 NLM ISO Abbreviation: World J Urol Subsets: MEDLINE

Original Publication: [Berlin ; New York] : Springer International, 1983-

Neoplasm Staging*; Carcinoma, Renal Cell/*metabolism ; Kidney Neoplasms/*metabolism ; Tubulin/*biosynthesis; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis ; Carcinoma, Renal Cell/diagnosis ; Carcinoma, Renal Cell/mortality ; Female ; Follow-Up Studies ; Germany/epidemiology ; Humans ; Immunohistochemistry ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/mortality ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate/trends ; Switzerland/epidemiology

Aims: βIII-tubulin (TUBB3) is a microtubule component overexpression of which is found in many solid cancer types, often linked to poor patient prognosis, and has been suggested to predict failure of microtubule-targeting chemotherapeutics. This study was designed to determine prevalence and prognostic impact of TUBB3 expression in kidney cancers.
Methods and Results: A tissue microarray (TMA) containing more than 1,200 renal tumors was analyzed by immunohistochemistry. TUBB3 expression varied markedly between the different histological subtypes and was more frequent in 105 papillary cancers (75.2 %, p < 0.0001), 38 oncocytomas (52.6 %, p < 0.0001), and 22 chromophobic carcinomas (36.4 %, p = 0.1221) than in 555 clear cell RCC (16.4 %). In clear cell cancers, strong TUBB3 positivity was linked to high Fuhrman grade (p < 0.0001), advanced stage (0.002), nodal metastases (p = 0.0433), hematogenous metastases (p = 0.0016), and shortened overall survival (p < 0.0001). Associations with outcome and tumor phenotype were inversely for papillary RCC, where TUBB3 immunostaining was linked to low tumor stage (p = 0.0012) and prolonged survival (p = 0.0043).
Conclusions: TUBB3 expression levels and their effects are strikingly different between ccRCC and papillary RCC. These differences may be caused by differences in VHL function between these RCC subtypes, because VHL (like TUBB3) is another strong regulator of microtubule function.

Am J Pathol. 1999 Apr;154(4):981-6. (PMID: 10233835)
J Thorac Oncol. 2010 Mar;5(3):320-5. (PMID: 20087230)
J Biol Chem. 1990 Jan 25;265(3):1794-9. (PMID: 2404018)
Methods Mol Med. 2005;114:257-68. (PMID: 16156109)
Eur J Cancer. 2013 Apr;49(6):1374-403. (PMID: 23485231)
Oncogene. 2003 Oct 20;22(47):7280-95. (PMID: 14576838)
Int J Cancer. 2006 May 1;118(9):2190-4. (PMID: 16331604)
Exp Cell Res. 2004 Dec 10;301(2):139-46. (PMID: 15530850)
Int J Cancer. 2013 Dec 15;133(12):2801-11. (PMID: 23740643)
Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3972-9. (PMID: 15217927)
Clin Cancer Res. 2011 Sep 15;17 (18):5878-88. (PMID: 21791629)
Cancer Res. 2004 Dec 15;64(24):8924-31. (PMID: 15604254)
Ann Oncol. 1994 Feb;5(2):185-7. (PMID: 7910480)
Clin Genitourin Cancer. 2009 Jan;7(1):39-42. (PMID: 19213667)
J Immunother Emphasis Tumor Immunol. 1993 May 4;13(4):275-81. (PMID: 8101452)
Lung Cancer. 2012 Jul;77(1):9-15. (PMID: 22306125)
CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300. (PMID: 20610543)
Mol Cancer Ther. 2005 Dec;4(12):2001-7. (PMID: 16373715)
Am J Surg Pathol. 1982 Oct;6(7):655-63. (PMID: 7180965)
Nature. 2010 Jan 21;463(7279):360-3. (PMID: 20054297)
Cell Motil Cytoskeleton. 1992;21(4):313-25. (PMID: 1628327)
Cell Motil Cytoskeleton. 2003 Jun;55(2):77-96. (PMID: 12740870)
Clin Cancer Res. 2013 Mar 15;19(6):1587-95. (PMID: 23340299)
J Clin Oncol. 1999 Mar;17(3):1061-70. (PMID: 10071301)
J Cell Biol. 2010 Sep 20;190(6):991-1003. (PMID: 20855504)
Eur J Cancer. 1994;30A(8):1064-7. (PMID: 7654430)
Mol Cancer Ther. 2012 May;11(5):1203-13. (PMID: 22411898)
Clin Cancer Res. 2005 May 1;11(9):3439-45. (PMID: 15867246)
J Pathol. 2001 Jul;194(3):349-57. (PMID: 11439368)
J Biol Chem. 1997 Jul 4;272(27):17118-25. (PMID: 9202030)
Hum Pathol. 2011 Jul;42(7):1019-26. (PMID: 21315408)
Am J Pathol. 2014 Mar;184(3):609-17. (PMID: 24378408)
Cytoskeleton (Hoboken). 2010 Apr;67(4):214-23. (PMID: 20191564)
J Cell Biol. 2010 May 3;189(3):541-56. (PMID: 20421424)
J Child Neurol. 2003 Dec;18(12):851-66; discussion 867. (PMID: 14736079)
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11358-62. (PMID: 7972064)
Cancer. 2012 Mar 1;118(5):1268-75. (PMID: 22161775)
Cancer Res. 2010 Nov 15;70(22):9253-64. (PMID: 21045157)
Tumour Biol. 2012 Oct;33(5):1759-65. (PMID: 22684772)
J BUON. 2012 Apr-Jun;17(2):284-90. (PMID: 22740207)
Br J Cancer. 2013 Jan 15;108(1):82-90. (PMID: 23321512)
Am J Pathol. 2001 Dec;159(6):2249-56. (PMID: 11733374)
Int J Cancer. 2007 May 15;120(10):2078-85. (PMID: 17285590)
Eur J Cancer. 2006 Sep;42(14):2296-302. (PMID: 16901687)
Gynecol Oncol. 2012 Apr;125(1):231-6. (PMID: 22209775)
Lancet Oncol. 2008 Feb;9(2):168-75. (PMID: 18237851)
Asia Pac J Clin Oncol. 2012 Sep;8(3):e42-8. (PMID: 22898150)
Anticancer Res. 2014 May;34(5):2255-61. (PMID: 24778028)
Cell Struct Funct. 1993 Jun;18(3):173-82. (PMID: 7902216)
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9552-6. (PMID: 8105478)

Keywords: Microtubules; Renal cell cancer; Survival; TMA; βIII-tubulin

0 (Biomarkers, Tumor)
0 (TUBB3 protein, human)
0 (Tubulin)

Clear-cell metastatic renal cell carcinoma

Date Created: 20141222 Date Completed: 20160719 Latest Revision: 20220311

20231215

10.1007/s00345-014-1463-6

25527909