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Open Access 01-12-2012 | Research

Clinical significance of clusterin expression in pancreatic adenocarcinoma

Authors: Junshuo Jin, Joon-Mee Kim, Yoon-Seok Hur, Won Pyo Cho, Keon-Young Lee, Seung-Ik Ahn, Kee Chun Hong, In-Sun Park

Published in: World Journal of Surgical Oncology | Issue 1/2012

Abstract

Background

Clusterin is known to be expressed in many human neoplasms, and is believed to participate in the regeneration, migration, and anti-apoptosis of tumor cells. However, few reports have addressed the relationship between the manifestation of clusterin and clinicopathologic parameters in pancreas cancer patients. In the present study, the authors investigated the expression of clusterin and its clinical significance in pancreatic adenocarcinoma.

Methods

Immunohistochemical staining was performed for clusterin in tumor tissues obtained from patients who received pancreatic resection with radical intent, and the associations of clusterin expression with various clinicopathologic parameters were analyzed in addition to the relation between its expression and survival.

Results

Immunoreactivity for clusterin was observed in 17 of the 52 (33%) pancreatic adenocarcinomas examined. In addition, clusterin positivity was found to be associated with preoperative serum carcinoembryonic antigen level, perineural invasion, and, most strongly, lymph node metastasis. The survival analysis identified tumor differentiation and lymph node metastasis as the only significant prognostic factors.

Conclusion

Although not an independent prognostic factor, clusterin immunoreactivity can be used in conjunction with lymph node metastasis to predict survival in cases of pancreatic adenocarcinoma.

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Lockhart AC, Rothenberg ML, Berlin JD: Treatment for pancreatic cancer: current therapy and continued progress. Gastroenterology. 2005, 128: 1642-1654. 10.1053/j.gastro.2005.03.039.CrossRefPubMed

Siegel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011, 61: 212-236. 10.3322/caac.20121.CrossRefPubMed

Dunphy EP: Pancreatic cancer: a review and update. Clin J Oncol Nurs. 2008, 12: 735-741. 10.1188/08.CJON.735-741.CrossRefPubMed

Jenne DE, Tschopp J: Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem Sci. 1992, 17: 154-159. 10.1016/0968-0004(92)90325-4.CrossRefPubMed

Xie MJ, Motoo Y, Su SB, Mouri H, Ohtsubo K, Matsubara F, Sawabu N: Expression of clusterin in human pancreatic cancer. Pancreas. 2002, 25: 234-238. 10.1097/00006676-200210000-00004.CrossRefPubMed

Rosenberg ME, Silkensen J: Clusterin: physiologic and pathophysiologic considerations. Int J Biochem Cell Biol. 1995, 27: 633-645. 10.1016/1357-2725(95)00027-M.CrossRefPubMed

Min BH, Kim BM, Lee SH, Kang SW, Bendayan M, Park IS: Clusterin expression in the early process of pancreas regeneration in the pancreatectomized rat. J Histochem Cytochem. 2003, 51: 1355-1365. 10.1177/002215540305101012.CrossRefPubMed

Cameron JL, Riall TS, Coleman J, Belcher KA: One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006, 244: 10-15. 10.1097/01.sla.0000217673.04165.ea.PubMedCentralCrossRefPubMed

Ozawa F, Friess H, Kunzli B, Shrikhande SV, Otani T, Makuuchi M, Buchler MW: Treatment of pancreatic cancer: the role of surgery. Dig Dis. 2001, 19: 47-56. 10.1159/000050653.CrossRefPubMed

10.

Pavlidis TE, Pavlidis ET, Sakantamis AK: Current opinion on lymphadenectomy in pancreatic cancer surgery. Hepatobiliary Pancreat Dis Int. 2011, 10: 21-25. 10.1016/S1499-3872(11)60002-7.CrossRefPubMed

11.

Sahin TT, Fujii T, Kanda M, Nagai S, Kodera Y, Kanzaki A, Yamamura K, Sugimoto H, Kasuya H, Nomoto S, Takeda S, Morita S, Nakao A: Prognostic implications of lymph node metastases in carcinoma of the body and tail of the pancreas. Pancreas. 2011, 40: 1029-1033. 10.1097/MPA.0b013e3182207893.CrossRefPubMed

12.

Kanda M, Fujii T, Sahin TT, Kanzaki A, Nagai S, Yamada S, Sugimoto H, Nomoto S, Takeda S, Kodera Y, Morita S, Nakao A: Invasion of the splenic artery is a crucial prognostic factor in carcinoma of the body and tail of the pancreas. Ann Surg. 2010, 251: 483-487. 10.1097/SLA.0b013e3181cf9171.CrossRefPubMed

13.

Tonini G, Pantano F, Vincenzi B, Gabbrielli A, Coppola R, Santini D: Molecular prognostic factors in patients with pancreatic cancer. Expert Opin Ther Targets. 2007, 11: 1553-1569. 10.1517/14728222.11.12.1553.CrossRefPubMed

14.

Viard I, Wehrli P, Jornot L, Bullani R, Vechietti JL, Schifferli JA, Tschopp J, French LE: Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. J Invest Dermatol. 1999, 112: 290-296. 10.1046/j.1523-1747.1999.00531.x.CrossRefPubMed

15.

Kruger S, Ola V, Fischer D, Feller AC, Friedrich M: Prognostic significance of clusterin immunoreactivity in breast cancer. Neoplasma. 2007, 54: 46-50.PubMed

16.

Yom CK, Woo HY, Min SY, Kang SY, Kim HS: Clusterin overexpression and relapse-free survival in breast cancer. Anticancer Res. 2009, 29: 3909-3912.PubMed

17.

Toffanin S, Daidone MG, Miodini P, De Cecco L, Gandellini P, Cappelletti V: Clusterin: a potential target for improving response to antiestrogens. Int J Oncol. 2008, 33: 791-798.PubMed

18.

Flanagan L, Whyte L, Chatterjee N, Tenniswood M: Effects of clusterin over-expression on metastatic progression and therapy in breast cancer. BMC Cancer. 2010, 10: 107-120. 10.1186/1471-2407-10-107.PubMedCentralCrossRefPubMed

19.

Redondo M, Villar E, Torres-Munoz J, Tellez T, Morell M, Petito CK: Overexpression of clusterin in human breast carcinoma. Am J Pathol. 2000, 157: 393-399. 10.1016/S0002-9440(10)64552-X.PubMedCentralCrossRefPubMed

20.

Zhang S, Zhang D, Zhu Y, Guo H, Zhao X, Sun B: Clusterin expression and univariate analysis of overall survival in human breast cancer. Technol Cancer Res Treat. 2006, 5: 573-578.CrossRefPubMed

21.

Steinberg J, Oyasu R, Lang S, Sintich S, Rademaker A, Lee C, Kozlowski JM, Sensibar JA: Intracellular levels of SGP-2 (clusterin) correlate with tumor grade in prostate cancer. Clin Cancer Res. 1997, 3: 1707-1711.PubMed

22.

July LV, Akbari M, Zellweger T, Jones EC, Goldenberg SL, Gleave ME: Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy. Prostate. 2002, 50: 179-188. 10.1002/pros.10047.CrossRefPubMed

23.

Chen Q, Wang Z, Zhang K, Liu X, Cao W, Zhang L, Zhang S, Yan B, Wang Y, Xia C: Clusterin confers gemcitabine resistance in pancreatic cancer. World J Surg Oncol. 2011, 24: 59-66.CrossRef

24.

Xie D, Lau SH, Sham JS, Wu QL, Fang Y, Liang LZ, Che LH, Zeng YX, Guan XY: Up-regulated expression of cytoplasmic clusterin in human ovarian carcinoma. Cancer. 2005, 103: 277-283. 10.1002/cncr.20765.CrossRefPubMed

25.

Partheen K, Levan K, Osterberg L, Claesson I, Fallenius G, Sundfeldt K, Horvath G: Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas. Int J Cancer. 2008, 123: 2130-2137. 10.1002/ijc.23758.CrossRefPubMed

26.

Yang GF, Li XM, Xie D: Overexpression of clusterin in ovarian cancer is correlated with impaired survival. Int J Gynecol Cancer. 2009, 19: 1342-1346. 10.1111/IGC.0b013e3181a83ed9.CrossRefPubMed

27.

Bi J, Guo AL, Lai YR, Li B, Zhong JM, Wu HQ, Xie Z, He YL, Lv ZL, Lau SH, Wang Q, Huang XH, Zhang LJ, Wen JM, Guan XY: Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays. Neoplasma. 2010, 57: 191-197. 10.4149/neo_2010_03_191.CrossRefPubMed

28.

Kevans D, Foley J, Tenniswood M, Sheahan K, Hyland J, O’Donoghue D, Mulcahy H, O’Sullivan J: High clusterin expression correlates with a poor outcome in stage II colorectal cancers. Cancer Epidemiol Biomarkers Prev. 2009, 18: 393-399. 10.1158/1055-9965.EPI-08-0302.CrossRefPubMed

29.

Redondo M, Rodrigo I, Alcaide J, Tellez T, Roldan MJ, Funez R, Diaz-Martin A, Rueda A, Jimenez E: Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomas. Histopathology. 2010, 56: 932-936. 10.1111/j.1365-2559.2010.03565.x.CrossRefPubMed

30.

Miyake H, Gleave ME, Arakawa S, Kamidono S, Hara I: Introducing the clusterin gene into human renal cell carcinoma cells enhances their metastatic potential. J Urol. 2002, 167: 2203-2208. 10.1016/S0022-5347(05)65129-4.CrossRefPubMed

31.

Cheng CY, Cherng SH, Wu WJ, Yang TY, Huang XY, Liao FT, Wu MF, Sheu GT: Regulation of chemosensitivity and migration by clusterin in non-small cell lung cancer cells. Cancer Chemother Pharmacol. 2012, 69: 145-154. 10.1007/s00280-011-1682-0.CrossRefPubMed

32.

Li H, Liu S, Zhu X, Yang S, Xiang J, Chen H: Clusterin immunoexpression and its clinical significance in patients with non-small cell lung cancer. Lung. 2010, 188: 423-431. 10.1007/s00408-010-9248-1.CrossRefPubMed

33.

Panico F, Rizzi F, Fabbri LM, Bettuzzi S, Luppi F: Clusterin (CLU) and lung cancer. Adv Cancer Res. 2009, 105: 63-76.CrossRefPubMed

34.

Sachs T, Pratt WB, Callery MP, Vollmer CM: The incidental asymptomatic pancreatic lesion: nuisance or threat?. J Gastrointest Surg. 2009, 13: 405-415. 10.1007/s11605-008-0788-0.CrossRefPubMed

Title: Clinical significance of clusterin expression in pancreatic adenocarcinoma
Authors: Junshuo Jin
Joon-Mee Kim
Yoon-Seok Hur
Won Pyo Cho
Keon-Young Lee
Seung-Ik Ahn
Kee Chun Hong
In-Sun Park
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2012
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/1477-7819-10-146

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Clinical significance of clusterin expression in pancreatic adenocarcinoma

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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