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Vol. 9, No. 1-2, 2009 

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Original Paper

Is Serous Cystadenoma of the Pancreas a Model of Clear-Cell-Associated Angiogenesis and Tumorigenesis?
Duangpen Thirabanjasaka, Olca Basturkb, Deniz Altinelc, Jeanette D. Chengd, N. Volkan Adsayc

Departments of Pathology,
aWayne State University and Karmanos Cancer Institute, Detroit, Mich.,
bNew York University, New York, N.Y.,
cEmory University and Winship Cancer Institute, and
dPiedmont Hospital, Atlanta, Ga., USA

Address of Corresponding Author

Pancreatology 2009;9:182-188 (DOI: 10.1159/000178890)


 goto top of outline Key Words

  • Pancreas
  • Serous cystadenoma
  • Angiogenesis
  • Clear cell

 goto top of outline Abstract

Background: Similar to the other von Hippel-Lindau (VHL)-related tumors such as renal cell carcinomas and capillary hemangioblastomas, serous cystadenomas (SCAs) of the pancreas are also characterized by clear cells. Over the years, we have also noticed that the tumor epithelium shows a prominent capillary network. Methods: Eighteen cases of SCA were reviewed histologically, and immunohistochemical analysis was performed for CD31 and vascular endothelial growth factor (VEGF) as well as the molecules implicated in clear-cell tumorigenesis: GLUT-1, hypoxia-inducible factor-1 (HIF-1alpha), and carbonic anhydrase IX (CA IX). Results: There was an extensively rich capillary network that appears almost intraepithelially in all cases of SCA, which was confirmed by CD31 stain that showed, on average, 26 capillaries per every 100 epithelial cells. VEGF expression was identified in 10/18 cases. Among the clear-cell tumorigenesis markers, CA IX was detected in all cases, GLUT-1 and HIF-1alpha in most cases. Conclusion: As in other VHL-related clear-cell tumors, there is a prominent capillary network immediately adjacent to the epithelium of SCA, confirming that the clear-cell- angiogenesis association is also valid for this tumor type. Molecules implicated in clear-cell tumorigenesis are also consistently expressed in SCA. This may have biologic and therapeutic implications, especially considering the rapidly evolving drugs against these pathways. More importantly, SCA may also serve as a model of clear-cell-associated angiogenesis and tumorigenesis, and the information gained from this tumor type may also be applicable to other clear-cell tumors.

Copyright © 2008 S. Karger AG, Basel and IAP


 goto top of outline References


1.
Adsay NV: Cystic neoplasia of the pancreas. Mod Pathol 2007;20:S71-S98.External Resources

2.
Yasuhara Y, Sakaida N, Uemura Y, Senzaki H, Shikata N, Tsubura A: Serous microcystic adenoma (glycogen-rich cystadenoma) of the pancreas: study of 11 cases showing clinicopathological and immunohistochemical correlations. Pathol Int 2002;52:307-312.External Resources

3.
Compagno J, Oertel JE: Microcystic adenomas of the pancreas (glycogen-rich cystadenomas): A clinicopathologic study of 34 cases. Am J Clin Pathol 1978;69:289-298.External Resources

4.
Warshaw AL, Compton CC, Lewandrowski K, Cardenosa G, Mueller PR: Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg 1990;212:432-445.External Resources

5.
Kloppel G, Kosmahl M: Cystic lesions and neoplasms of the pancreas. The features are becoming clearer. Pancreatology 2001;1:648-655.External Resources

6.
Fernandez-del Castillo C, Warshaw AL: Cystic neoplasms of the pancreas. Pancreatology 2001;1:641-647.External Resources

7.
Shorten SD, Hart WR, Petras RE: Microcystic adenomas (serous cystadenomas) of pancreas. A clinicopathologic investigation of eight cases with immunohistochemical and ultrastructural studies. Am J Surg Pathol 1986;10:365-372.External Resources

8.
Alpert LC, Truong LD, Bossart MI, Spjut HJ: Microcystic adenoma (serous cystadenoma) of the pancreas. A study of 14 cases with immunohistochemical and electron-microscopic correlation. Am J Surg Pathol 1988;12:251-263.External Resources

9.
Bogomoletz WV, Adnet JJ, Widgren S, Stavrou M, McLaughlin JE: Cystadenoma of the pancreas: A histological, histochemical and ultrastructural study of seven cases. Histopathology 1980;4:309-320.External Resources

10.
Kosmahl M, Pauser U, Anlauf M, Sipos B, Peters K, Luttges J, Kloppel G: [Cystic pancreas tumors and their classification: features old and new]. Pathologe 2005;26:22-30.External Resources

11.
Compton CC: Serous cystic tumors of the pancreas. Semin Diagn Pathol 2000;17:43-55.External Resources

12.
George DH, Murphy F, Michalski R, Ulmer BG: Serous cystadenocarcinoma of the pancreas: A new entity? Am J Surg Pathol 1989;13:61-66.External Resources

13.
Yoshimi N, Sugie S, Tanaka T, Aijin W, Bunai Y, Tatematsu A, Okada T, Mori H: A rare case of serous cystadenocarcinoma of the pancreas. Cancer 1992;69:2449-2453.External Resources

14.
Mohr VH, Vortmeyer AO, Zhuang Z, Libutti SK, Walther MM, Choyke PL, Zbar B, Linehan WM, Lubensky IA: Histopathology and molecular genetics of multiple cysts and microcystic (serous) adenomas of the pancreas in von Hippel-Lindau patients. Am J Pathol 2000;157:1615-1621.External Resources

15.
Moore PS, Zamboni G, Brighenti A, Lissandrini D, Antonello D, Capelli P, Rigaud G, Falconi M, Scarpa A: Molecular characterization of pancreatic serous microcystic adenomas: Evidence for a tumor suppressor gene on chromosome 10q. Am J Pathol 2001;158:317-321.External Resources

16.
Vortmeyer AO, Lubensky IA, Fogt F, Linehan WM, Khettry U, Zhuang Z: Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. Am J Pathol 1997;151:951-956.External Resources

17.
Neumann HP, Dinkel E, Brambs H, Wimmer B, Friedburg H, Volk B, Sigmund G, Riegler P, Haag K, Schollmeyer P, et al: Pancreatic lesions in the von Hippel-Lindau syndrome. Gastroenterology 1991;101:465-471.External Resources

18.
Friedrich CA: Von Hippel-Lindau syndrome. A pleomorphic condition. Cancer 1999;86:2478-2482.External Resources

19.
Melmon KL, Rosen SW: Lindau's disease. Review of the literature and study of a large kindred. Am J Med 1964;36:595-617.External Resources

20.
Horton WA, Wong V, Eldridge R: Von Hippel-Lindau disease: Clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med 1976;136:769-777.External Resources

21.
George DJ, Kaelin WG Jr: The von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer. N Engl J Med 2003;349:419-421.External Resources

22.
Isselbacher KJ: Sugar and amino acid transport by cells in culture - differences between normal and malignant cells. N Engl J Med 1972;286:929-933.External Resources

23.
Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, Yamada Y, Inoue K, Manabe T, Imura H: Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990;170:223-230.External Resources

24.
Haber RS, Rathan A, Weiser KR, Pritsker A, Itzkowitz SH, Bodian C, Slater G, Weiss A, Burstein DE: Glut1 glucose transporter expression in colorectal carcinoma: A marker for poor prognosis. Cancer 1998;83:34-40.External Resources

25.
Ito T, Noguchi Y, Satoh S, Hayashi H, Inayama Y, Kitamura H: Expression of facilitative glucose transporter isoforms in lung carcinomas: Its relation to histologic type, differentiation grade, and tumor stage. Mod Pathol 1998;11:437-443.External Resources

26.
Ito H, Duxbury M, Zinner MJ, Ashley SW, Whang EE: Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activity. Surgery 2004;136:548-556.External Resources

27.
Kang SS, Chun YK, Hur MH, Lee HK, Kim YJ, Hong SR, Lee JH, Lee SG, Park YK: Clinical significance of glucose transporter 1 (glut1) expression in human breast carcinoma. Jpn J Cancer Res 2002;93:1123-1128.External Resources

28.
Kawamura T, Kusakabe T, Sugino T, Watanabe K, Fukuda T, Nashimoto A, Honma K, Suzuki T: Expression of glucose transporter-1 in human gastric carcinoma: Association with tumor aggressiveness, metastasis, and patient survival. Cancer 2001;92:634-641.External Resources

29.
Reisser C, Eichhorn K, Herold-Mende C, Born AI, Bannasch P: Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. Int J Cancer 1999;80:194-198.External Resources

30.
Younes M, Juarez D, Lechago LV, Lerner SP: Glut 1 expression in transitional cell carcinoma of the urinary bladder is associated with poor patient survival. Anticancer Res 2001;21:575-578.External Resources

31.
Bui MH, Visapaa H, Seligson D, Kim H, Han KR, Huang Y, Horvath S, Stanbridge EJ, Palotie A, Figlin RA, Belldegrun AS: Prognostic value of carbonic anhydrase IX and Ki67 as predictors of survival for renal clear cell carcinoma. J Urol 2004;171:2461-2466.External Resources

32.
Dorai T, Sawczuk IS, Pastorek J, Wiernik PH, Dutcher JP: The role of carbonic anhydrase IX overexpression in kidney cancer. Eur J Cancer 2005;41:2935-2947.External Resources

33.
Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y, Horvath S, Leibovich BC, Chopra S, Liao SY, Stanbridge E, Lerman MI, Palotie A, Figlin RA, Belldegrun AS: Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 2003;9:802-811.External Resources

34.
Leppert JT, Lam JS, Pantuck AJ, Figlin RA, Belldegrun AS: Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma. BJU Int 2005;96:281-285.External Resources

35.
Uemura H, Cho M, Nakagawa Y, Shimizu K, Yoshikawa M, Kim S, Hirao Y: [MN/CA IX antigen as a potential target for renal cell carcinoma]. Hinyokika Kiyo 2000;46:745-748.External Resources

36.
Bismar TA, Bianco FJ, Zhang H, Li X, Sarkar FH, Sakr WA, Grignon DJ, Che M: Quantification of G250 MRNA expression in renal epithelial neoplasms by real-time reverse transcription-PCR of dissected tissue from paraffin sections. Pathology 2003;35:513-517.External Resources

37.
Jiang YD, Zheng SB, Wang ZH: [Detection of carbonic anhydrase IX gene expression in renal cell carcinoma with reverse transcription-PCR]. Di Yi Jun Yi Da Xue Xue Bao 2004;24:99-101.External Resources

38.
Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A, Wilson GD, Turley H, Talks KL, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL: Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 2000;60:7075-7083.External Resources

39.
Yamazaki K, Eyden B: An immunohistochemical and ultrastructural study of pancreatic microcystic serous cyst adenoma with special reference to tumor-associated microvasculature and vascular endothelial growth factor in tumor cells. Ultrastruct Pathol 2006;30:119-128.External Resources

40.
Nagase Y, Takata K, Moriyama N, Aso Y, Murakami T, Hirano H: Immunohistochemical localization of glucose transporters in human renal cell carcinoma. J Urol 1995;153:798-801.External Resources

41.
Giaccone G: The potential of antiangiogenic therapy in non-small cell lung cancer. Clin Cancer Res 2007;13:1961-1970.External Resources

42.
Longo R, Gasparini G: Challenges for patient selection with VEGF inhibitors. Cancer Chemother Pharmacol 2007;60:151-170.External Resources

43.
Shih T, Lindley C: Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 2006;28:1779-1802.External Resources

44.
Johnson BF, Clay TM, Hobeika AC, Lyerly HK, Morse MA: Vascular endothelial growth factor and immunosuppression in cancer: Current knowledge and potential for new therapy. Expert Opin Biol Ther 2007;7:449-460.External Resources

45.
Bassi C, Salvia R, Molinari E, Biasutti C, Falconi M, Pederzoli P: Management of 100 consecutive cases of pancreatic serous cystadenoma: Wait for symptoms and see at imaging or vice versa? World J Surg 2003;27:319-323.External Resources

46.
Tseng JF, Warshaw AL, Sahani DV, Lauwers GY, Rattner DW, Fernandez-del Castillo C: Serous cystadenoma of the pancreas: Tumor growth rates and recommendations for treatment. Ann Surg 2005;242:413-421.External Resources


 goto top of outline Author Contacts

N. Volkan Adsay, MD
Emory University Hospital and Winship Cancer Institute
Department of Pathology, Room H-185-B
1364 Clifton Road NE, Atlanta, GA 30322 (USA)
Tel. +1 404 712 4179, Fax +1 404 712 8802, E-Mail volkan.adsay@emory.edu


 goto top of outline Article Information

Received: December 31, 2007
Accepted after revision: July 2, 2008
Published online: December 13, 2008
Number of Print Pages : 7
Number of Figures : 7, Number of Tables : 2, Number of References : 46


 goto top of outline Publication Details

Pancreatology

Vol. 9, No. 1-2, Year 2009 (Cover Date: April 2009)

Journal Editor: Urrutia R. (Rochester, Minn.)
ISSN: 1424-3903 (Print), eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN


 goto top of outline Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.

   


copyright  © 2009 S. Karger AG, Basel
  Last update: 7/4/2009