CD44 is associated with tumor recurrence and is an independent poor prognostic factor for patients with localized clear cell renal cell carcinoma after nephrectomy

Jeong,Byung-Joo; Liang,Zhe Long; Huang,Song Mei; Lim,Jae Sung; Kim,Jin Man; Lee,Hyo Jin

doi:10.3892/etm.2012.505

CD44 is associated with tumor recurrence and is an independent poor prognostic factor for patients with localized clear cell renal cell carcinoma after nephrectomy

Authors:
- Byung-Joo Jeong
- Zhe Long Liang
- Song Mei Huang
- Jae Sung Lim
- Jin Man Kim
- Hyo Jin Lee
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Affiliations: Department of Pathology, Cancer Research Institute and Infection Signaling Network Research Center, Chungnam National Univerisity School of Medicine, Daejeon, Republic of Korea, Department of Urology, Chungnam National University School of Medicine, Daejeon, Republic of Korea, Department of Internal Medicine and Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea
Published online on: March 5, 2012 https://doi.org/10.3892/etm.2012.505
Pages: 811-817

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Abstract

CD44 has been implicated in tumor development and progression in several types of cancer. CD44 expression is altered in renal cell carcinoma (RCC) and has been suggested as a useful prognostic marker, but its prognostic role in RCC remains controversial. We investigated the expression of CD44 in a large homogeneous set of localized clear cell RCC to determine its potential prognostic value. We examined 110 patients with localized clear cell RCC who underwent nephrectomy. The clinicopathological data were obtained retrospectively and the expression level of CD44 was studied by immunohistochemistry. Correlations between CD44 expression and clinical parameters as well as survival were determined. The CD44-high expression group (HEG) was significantly associated with a higher nuclear grade (P=0.014) and tumor recurrence (P<0.001) when compared with the CD44-low expression group (LEG). Concerning survival, the 5-year recurrence-free survival (RFS) rates for the CD44-HEG and CD44-LEG groups were 38.9 and 91.3%, respectively (P<0.001), and the 5-year disease-specific survival (DSS) rates for the CD44-HEG and CD44-LEG groups were 55.6 and 94.6%, respectively (P<0.001). Multivariate analyses showed that CD44 expression [hazard ratio (HR), 9.204; P<0.001] was an independent risk factor predicting RFS in patients with clear cell RCC. CD44 expression remained an independent prognostic factor for DSS (P=0.002). In conclusion, these data indicate that CD44 expression is associated with the progression of clear cell RCC and is an independent poor prognostic factor for tumor recurrence and survival, suggesting that CD44 may serve as a useful molecular marker.

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1.	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2.	Crispen PL, Boorjian SA, Lohse CM, Leibovich BC and Kwon ED: Predicting disease progression after nephrectomy for localized renal cell carcinoma: the utility of prognostic models and molecular biomarkers. Cancer. 113:450–460. 2008. View Article : Google Scholar : PubMed/NCBI
3.	Zisman A, Pantuck AJ, Wieder J, et al: Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol. 20:4559–4566. 2002. View Article : Google Scholar : PubMed/NCBI
4.	Klatte T, Seligson DB, Leppert JT, et al: The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma. J Urol. 179:61–66. 2008. View Article : Google Scholar : PubMed/NCBI
5.	Motzer RJ, Hutson TE, Tomczak P, et al: Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 27:3584–3590. 2009. View Article : Google Scholar : PubMed/NCBI
6.	Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL and Zincke H: An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol. 168:2395–2400. 2002. View Article : Google Scholar : PubMed/NCBI
7.	Patard JJ, Kim HL, Lam JS, et al: Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol. 22:3316–3322. 2004. View Article : Google Scholar : PubMed/NCBI
8.	Zisman A, Pantuck AJ, Dorey F, et al: Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 19:1649–1657. 2001.PubMed/NCBI
9.	Lam JS, Klatte T, Kim HL, et al: Prognostic factors and selection for clinical studies of patients with kidney cancer. Crit Rev Oncol Hematol. 65:235–262. 2008. View Article : Google Scholar : PubMed/NCBI
10.	Volpe A and Patard JJ: Prognostic factors in renal cell carcinoma. World J Urol. 28:319–327. 2010. View Article : Google Scholar
11.	Marhaba R and Zoller M: CD44 in cancer progression: adhesion, migration and growth regulation. J Mol Histol. 35:211–231. 2004. View Article : Google Scholar : PubMed/NCBI
12.	Naor D, Sionov RV and Ish-Shalom D: CD44: structure, function, and association with the malignant process. Adv Cancer Res. 71:241–319. 1997. View Article : Google Scholar : PubMed/NCBI
13.	Tawfik OW, Kramer B, Shideler B, Danley M, Kimler BF and Holzbeierlein J: Prognostic significance of CD44, platelet-derived growth factor receptor alpha, and cyclooxygenase 2 expression in renal cell carcinoma. Arch Pathol Lab Med. 131:261–267. 2007.PubMed/NCBI
14.	Liao HX, Lee DM, Levesque MC and Haynes BF: N-terminal and central regions of the human CD44 extracellular domain participate in cell surface hyaluronan binding. J Immunol. 155:3938–3945. 1995.PubMed/NCBI
15.	Lim SD, Young AN, Paner GP and Amin MB: Prognostic role of CD44 cell adhesion molecule expression in primary and metastatic renal cell carcinoma: a clinicopathologic study of 125 cases. Virchows Arch. 452:49–55. 2008. View Article : Google Scholar : PubMed/NCBI
16.	Bamias A, Chorti M, Deliveliotis C, et al: Prognostic significance of CA 125, CD44, and epithelial membrane antigen in renal cell carcinoma. Urology. 62:368–373. 2003. View Article : Google Scholar : PubMed/NCBI
17.	Wu ST, Sun GH, Hsieh DS, Chen A, Chen HI, Chang SY and Yu D: Correlation of CD44v5 expression with invasiveness and prognosis in renal cell carcinoma. J Formos Med Assoc. 102:229–233. 2003.PubMed/NCBI
18.	Paradis V, Ferlicot S, Ghannam E, et al: CD44 is an independent prognostic factor in conventional renal cell carcinomas. J Urol. 16:1984–1987. 1999. View Article : Google Scholar
19.	Rioux-Leclercq N, Epstein JI, Bansard JY, et al: Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma. Hum Pathol. 32:1209–1215. 2001. View Article : Google Scholar : PubMed/NCBI
20.	Lucin K, Matusan K, Dordević G and Stipić D: Prognostic significance of CD44 molecule in renal cell carcinoma. Croat Med J. 45:703–708. 2004.PubMed/NCBI
21.	Gilcrease MZ, Guzman-Paz M, Niehans G, Cherwitz D, McCarthy JB and Albores-Saavedra J: Correlation of CD44S expression in renal clear cell carcinomas with subsequent tumor progression or recurrence. Cancer. 86:2320–2326. 1999. View Article : Google Scholar : PubMed/NCBI
22.	Heider KH, Ratschek M, Zatloukal K and Adolf GR: Expression of CD44 isoforms in human renal cell carcinomas. Virchows Arch. 428:267–273. 1996.PubMed/NCBI
23.	Matusan K, Dordevic G, Mozetic V and Lucin K: Expression of osteopontin and CD44 molecule in papillary renal cell tumors. Pathol Oncol Res. 11:108–113. 2005. View Article : Google Scholar : PubMed/NCBI
24.	Lee SM, Lee KE, Chang HJ, et al: Prognostic significance of CD44s expression in biliary tract cancers. Ann Surg Oncol. 15:1155–1160. 2008. View Article : Google Scholar : PubMed/NCBI
25.	Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y and Wang TC: Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 27:1006–1020. 2009. View Article : Google Scholar : PubMed/NCBI
26.	Zeilstra J, Joosten SP, Dokter M, Verwiel E, Spaargaren M and Pals ST: Deletion of the WNT target and cancer stem cell marker CD44 in Apc(Min/⁺) mice attenuates intestinal tumorigenesis. Cancer Res. 68:3655–3661. 2008. View Article : Google Scholar : PubMed/NCBI
27.	Jin L, Hope KJ, Zhai Q, Smadja-Joffe F and Dick JE: Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 12:1167–1174. 2006. View Article : Google Scholar : PubMed/NCBI
28.	Krause DS, Lazarides K, von Andrian UH and van Etten RA: Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat Med. 12:1175–1180. 2006. View Article : Google Scholar : PubMed/NCBI
29.	Huh JW, Kim HR, Kim YJ, Lee JH, Park YS, Cho SH and Joo JK: Expression of standard CD44 in human colorectal carcinoma: association with prognosis. Pathol Int. 59:241–246. 2009. View Article : Google Scholar : PubMed/NCBI
30.	Terpe HJ, Störkel S, Zimmer U, Anquez V, Fischer C, Pantel K and Günthert U: Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation. Am J Pathol. 148:453–463. 1996.PubMed/NCBI
31.	Zolota V, Tsamandas AC, Melachrinou M, Batistatou A and Scopa C: Expression of CD44 protein in renal cell carcinomas: association with p53 expression. Urol Oncol. 7:13–17. 2002. View Article : Google Scholar : PubMed/NCBI