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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2010 | Research

Evaluation of myosin VI, E-cadherin and beta-catenin immunostaining in renal cell carcinoma

Authors: Hanna Ronkainen, Saila Kauppila, Pasi Hirvikoski, Markku H Vaarala

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2010

Abstract

Background

Renal cell carcinoma (RCC) is a cancer of increasing incidence and mortality. Currently, there are no immunohistochemical prognostic markers for RCCs in routine use. The aim of this study was to examine for the first time the immunostaining of myosin VI in RCCs as well as its association with E-cadherin and beta-catenin immunostaining and the prognostic significance of these markers in RCCs.

Methods

Our study population consisted of 152 patients who underwent surgery for RCCs between 1990 and 1999. The tumours were examined with three immunohistochemical markers: myosin VI, E-cadherin and beta-catenin.

Results

The immunostaining for cytoplasmic myosin VI was common (72%). One-third of the tumours were immunopositive for nuclear myosin VI. Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades (p = 0.04 and p = 0.005, respectively), but not stages. There was no significant association between myosin VI immunostaining and the histological subtype of RCC. Nuclear myosin VI was associated with the nuclear expression of beta-catenin. A direct association could also be proven between membranous E-cadherin and cytoplasmic beta-catenin. Cytoplasmic myosin VI immunostaining was a marker of poorer prognosis in multivariate Cox regression model adjusted with stage and Fuhrman grade with hazard ratio 2.4 (95% confidence interval 1.1 to 5.0 with p = 0.024).

Conclusions

Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades, and there was a strong positive relationship between E-cadherin immunostaining and beta-catenin immunostaining in RCCs. Cytoplasmic myosin VI immunostaining was associated with poorer prognosis in RCCs.

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Pantuck AJ, Zisman A, Belldegrun AS: The changing natural history of renal cell carcinoma. J Urol. 2001, 166: 1611-1623. 10.1016/S0022-5347(05)65640-6.CrossRef

Bui MH, Zisman A, Pantuck AJ, Han KR, Wieder J, Belldegrun AS: Prognostic factors and molecular markers for renal cell carcinoma. Expert Rev Anticancer Ther. 2001, 1: 565-575. 10.1586/14737140.1.4.565.CrossRef

Wells AL, Lin AW, Chen LQ, Safer D, Cain SM, Hasson T, Carragher BO, Milligan RA, Sweeney HL: Myosin VI is an actin-based motor that moves backwards. Nature. 1999, 401: 505-508. 10.1038/46835.CrossRef

Macartney JC, Trevithick MA, Kricka L, Curran RC: Identification of myosin in human epithelial cancers with immunofluorescence. Lab Invest. 1979, 41: 437-445.

Buss F, Kendrick-Jones J: How are the cellular functions of myosin VI regulated within the cell?. Biochem Biophys Res Commun. 2008, 369: 165-175. 10.1016/j.bbrc.2007.11.150.CrossRef

Sweeney HL, Houdusse A: What can myosin VI do in cells?. Curr Opin Cell Biol. 2007, 19: 57-66. 10.1016/j.ceb.2006.12.005.CrossRef

Geisbrecht ER, Montell DJ: Myosin VI is required for E-cadherin-mediated border cell migration. Nat Cell Biol. 2002, 4: 616-620.

Meyer T, Hart IR: Mechanisms of tumour metastasis. Eur J Cancer. 1998, 34: 214-221. 10.1016/S0959-8049(97)10129-0.CrossRef

Takeichi M: The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988, 102: 639-655.

10.

Sommers CL, Thompson EW, Torri JA, Kemler R, Gelmann EP, Byers SW: Cell adhesion molecule uvomorulin expression in human breast cancer cell lines: relationship to morphology and invasive capacities. Cell Growth Differ. 1991, 2: 365-372.

11.

Doki Y, Shiozaki H, Tahara H, Inoue M, Oka H, Iihara K, Kadowaki T, Takeichi M, Mori T: Correlation between E-cadherin expression and invasiveness in vitro in a human esophageal cancer cell line. Cancer Res. 1993, 53: 3421-3426.

12.

Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, Debruyne FM, Schalken JA: Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 1994, 54: 3929-3933.

13.

Bringuier PP, Umbas R, Schaafsma HE, Karthaus HF, Debruyne FM, Schalken JA: Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 1993, 53: 3241-3245.

14.

Dorudi S, Sheffield JP, Poulsom R, Northover JM, Hart IR: E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study. Am J Pathol. 1993, 142: 981-986.

15.

Gervais ML, Henry PC, Saravanan A, Burry TN, Gallie BL, Jewett MA, Hill RP, Evans AJ, Ohh M: Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma. Lab Invest. 2007, 87: 1252-1264. 10.1038/labinvest.3700684.CrossRef

16.

Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W: Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996, 382: 638-642. 10.1038/382638a0.CrossRef

17.

Karim R, Tse G, Putti T, Scolyer R, Lee S: The significance of the Wnt pathway in the pathology of human cancers. Pathology. 2004, 36: 120-128. 10.1080/00313020410001671957.CrossRef

18.

Ronkainen H, Vaarala MH, Kauppila S, Soini Y, Paavonen TK, Rask J, Hirvikoski P: Increased BTB-Kelch type substrate adaptor protein immunoreactivity associates with advanced stage and poor differentiation in renal cell carcinoma. Oncol Rep. 2009, 21: 1519-1523.

19.

UICC: TNM Classification of Malignant Tumours. 2002, Wiley & Sons, New York, 6

20.

IARC: Tumours of the Urinary System and Male Genital Organs. 2004, IARC Press, Lyon

21.

Dunn TA, Chen S, Faith DA, Hicks JL, Platz EA, Chen Y, Ewing CM, Sauvageot J, Isaacs WB, De Marzo AM, Luo J: A novel role of myosin VI in human prostate cancer. Am J Pathol. 2006, 169: 1843-1854. 10.2353/ajpath.2006.060316.CrossRef

22.

Loikkanen I, Toljamo K, Hirvikoski P, Vaisanen T, Paavonen TK, Vaarala MH: Myosin VI is a modulator of androgen-dependent gene expression. Oncol Rep. 2009, 22: 991-995.

23.

McGurk L, Tzolovsky G, Spears N, Bownes M: The temporal and spatial expression pattern of myosin Va, Vb and VI in the mouse ovary. Gene Expr Patterns. 2006, 6: 900-907. 10.1016/j.modgep.2006.03.002.CrossRef

24.

Yoshida H, Cheng W, Hung J, Montell D, Geisbrecht E, Rosen D, Liu J, Naora H: Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer. Proc Natl Acad Sci USA. 2004, 101: 8144-8149. 10.1073/pnas.0400400101.CrossRef

25.

Guo L, Kuroda N, Miyazaki E, Hayashi Y, Toi M, Naruse K, Hiroi M, Ashida S, Shuin T, Enzan H: The complementary role of beta-catenin in diagnosing various subtypes of renal cell carcinomas and its up-regulation in conventional renal cell carcinomas with high nuclear grades. Oncol Rep. 2001, 8: 521-526.

26.

Evans AJ, Russell RC, Roche O, Burry TN, Fish JE, Chow VW, Kim WY, Saravanan A, Maynard MA, Gervais ML, Sufan RI, Roberts AM, Wilson LA, Betten M, Vandewalle C, Berx G, Marsden PA, Irwin MS, Teh BT, Jewett MA, Ohh M: VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail. Mol Cell Biol. 2007, 27: 157-169. 10.1128/MCB.00892-06.CrossRef

27.

Iwamoto M, Ahnen DJ, Franklin WA, Maltzman TH: Expression of beta-catenin and full-length APC protein in normal and neoplastic colonic tissues. Carcinogenesis. 2000, 21: 1935-1940. 10.1093/carcin/21.11.1935.CrossRef

28.

Bian YS, Osterheld MC, Bosman FT, Fontolliet C, Benhattar J: Nuclear accumulation of beta-catenin is a common and early event during neoplastic progression of Barrett esophagus. Am J Clin Pathol. 2000, 114: 583-590. 10.1309/3QLC-5MF1-JYXU-A5XX.CrossRef

29.

Ougolkov A, Mai M, Takahashi Y, Omote K, Bilim V, Shimizu A, Minamoto T: Altered expression of beta-catenin and c-erbB-2 in early gastric cancer. J Exp Clin Cancer Res. 2000, 19: 349-355.

30.

Saegusa M, Hashimura M, Yoshida T, Okayasu I: beta-Catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br J Cancer. 2001, 84: 209-217. 10.1054/bjoc.2000.1581.CrossRef

31.

Han AC, Soler AP, Tang CK, Knudsen KA, Salazar H: Nuclear localization of E-cadherin expression in Merkel cell carcinoma. Arch Pathol Lab Med. 2000, 124: 1147-1151.

32.

Serra S, Salahshor S, Fagih M, Niakosari F, Radhi JM, Chetty R: Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas. JOP. 2007, 8: 296-303.

Title: Evaluation of myosin VI, E-cadherin and beta-catenin immunostaining in renal cell carcinoma
Authors: Hanna Ronkainen
Saila Kauppila
Pasi Hirvikoski
Markku H Vaarala
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2010
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/1756-9966-29-2

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