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Digestive Diseases and Sciences

, Volume 49, Issue 11–12, pp 1906–1911 | Cite as

Cyclooxygenase-2 Expression in the Hereditary Mixed Polyposis Syndrome

  • Eli Brazowski
  • Faina Misonzhnick-Bedny
  • Paul RozenEmail author
Article

Abstract

Hereditary mixed polyposis syndrome (HMPS), characterized by hyperplastic, juvenile, admixed, serrated adenomas and eventually colorectal cancer, is managed by repeated polypectomy and surgery. We determined if HMPS polyps express cyclooxygenase-2 (COX-2). Nineteen recent HMPS polyps, from five family members, were stained for COX-2. Polyps’ epithelium and stroma and comparison tissues (normal colonic mucosa [9], sporadic juvenile polyps [18], colorectal cancers [3]) were quantified for COX-2 by: area of staining (0–3) × intensity (0–3). Epithelial, stromal, and total scores were evaluated in relationship to histology and dysplasia. HMPS polyps COX-2 mean epithelial (5.0 ± 3.0), stromal (6.9 ± 1.9), and total (11.8 ± 4.6) scores were significantly higher (P&<0.01) than sporadic juvenile polyps (0.6 ± 0.7, 3.1 ± 2.2, and 3.6 ± 2.2 respectively), while colorectal cancer scored 9, 9, and 18. There was a positive association (P&<0.01) among histology, degree of dysplasia, and COX-2 expression. COX-2 expression in HMPS polyps and its association with dysplasia suggest that chemoprevention might be a useful adjunct therapy.

chemoprevention colorectal cancer COX-2 familial polyps 

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References

  1. 1.
    Jaeger EEM, Woodford-Richens KL, Lockett M, Rowan AJ, Sawyer EJ, Heinimann K, Rozen P, Murday VA, Whitelaw SC, Ginsberg A, Atkin WS, Lynch HT, Southey MC, Debinski H, Eng C, Bodmer WF, Talbot IC, Hodgson SV, Thomas HJW, Tomlinson IPM: An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with Hereditary Mixed Polyposis Syndrome. Am J Hum Genet 72:1261–1267, 2003CrossRefGoogle Scholar
  2. 2.
    Rozen P, Samuel Z, Brazowski E: A prospective study of the clinical, genetic, screening and pathological features of a family with hereditary mixed polyposis syndrome. Am J Gastroenterol 98:2317–2320, 2003CrossRefGoogle Scholar
  3. 3.
    Steinbach G, Lynch PM, Philips RKS, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946–1952, 2000CrossRefGoogle Scholar
  4. 4.
    Rossi DJ, Ylikorkala A, Korsisaari N, Salovaara R, Luukko K, Launonen V, Henkemeyer, Ristimäki A, Aaltonen LA, Mäkelä TP: Induction of cyclooxygenase-2 in a mouse model of Peutz-Jegher polyposis. Proc Natl Acad Sci USA 99:12327–12332, 2002Google Scholar
  5. 5.
    McGarrity TJ, Peiffer LP, Amos CI, Frazier ML, Ward MG, Howett MK: Overexpression of cyclooxygenase 2 in hamartomatous polyps of Peutz-Jeghers Syndrome. Am J Gastroenterol 98:671–678, 2003CrossRefGoogle Scholar
  6. 6.
    Rozen P, Samuel Z, Brazowski E, Jakubowicz M, Rattan J, Halpern Z: An audit of familial juvenile polyposis at the Tel Aviv Medical Center: demographic, genetic and clinical features. Fam Cancer 2:1–7, 2003CrossRefGoogle Scholar
  7. 7.
    Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM: Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps. Cancer Res 62:6846–6849, 2002PubMedGoogle Scholar
  8. 8.
    Takeda H, Sonoshita M, Oshima H, Sugihara K-I, Chulada PC, Langenbach R, Oshima M, Taketo MM: Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis. Cancer Res 63:4872–4877, 2003PubMedGoogle Scholar
  9. 9.
    Kune GA, Kune S, Watson LF: Colorectal cancer risk, chronic illnesses, operations, and medications: Case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48:4399–4404, 1988PubMedGoogle Scholar
  10. 10.
    Thun MJ, Namboodiri MM, Heath CW Jr: Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596, 1991CrossRefGoogle Scholar
  11. 11.
    Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztess R, Petrelli N, Pipas JM, Karp DD, Loprinzi CL, Steinbach G, Schilsky R: A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 348:883–890, 2003CrossRefGoogle Scholar
  12. 12.
    Benamouzig R, Deyra J, Martin A, Girard B, Julian E, Piednoir B, Couturier D, Coste T, Little J, Chaussade S, for The Association Pour La Prevention Par L’ Aspirine due Cancer Colorectal Study Group: Daily soluble aspirin and prevention of colorectal adenoma recurrence: One-year results of the APACC trial. Gastroenterology 125:328–336, 2003CrossRefGoogle Scholar
  13. 13.
    Sørensen HT, Friis S, Nørgård B, Mellemkjær L, Blot WJ, McLaughlin JK, Ekbom A, Baron JA: Risk of cancer in a large cohort of nonaspirin NSAID users: A population-based study. Br J Cancer 88:1687–1692, 2003CrossRefGoogle Scholar
  14. 14.
    Arao J, Sano Y, Fujii T, Shigeharu K, Fu KI, Yoshino T, Ochiai A, Fujimori T, Yoshida S: Cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum. Dis Colon Rectum 44:1319–1323, 2001CrossRefGoogle Scholar
  15. 15.
    Takeuchi M, Kobayashi M, Ajioka Y, Honma T, Suzuki Y, Azumaya M, Narisawa R, Hayashi S-I, Asakura H: Comparison of cyclo-oxygenase 2 expression in colorectal serrated adenomas to expression in tubular adenomas and hyperplastic polyps. Int J Colorectal Dis 17:144–149, 2002CrossRefGoogle Scholar
  16. 16.
    Kawada M, Seno H, Wada M, Suzuki K, Kanda N, Kayahara T, Fukui H, Sawada M, Kajiyama T, Sakai M, Chiba T: Cyclooxygenase-2 expression and angiogenesis in gastric hyperplastic polyp—Association with polyp size. Digestion 67:20–24, 2003CrossRefGoogle Scholar
  17. 17.
    Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor ACJ, Guillou PJ, Markham AF, Coletta PL, Hull MA: Localization of cyclooxygenase-2 in human sporadic colorectal adenomas. Am J Pathol 156:545–553, 2000CrossRefGoogle Scholar
  18. 18.
    Sato T, Yoshinaga K, Okabe S, Enomoto M, Takizawa T, Sugihara K: Cyclooxygenase-2 expression in colorectal adenomas. Dis Colon Rectum 46:786–792, 2003CrossRefGoogle Scholar
  19. 19.
    Einspahr JG, Krouse RS, Yochim JM, Danenberg PV, Danenberg KD, Bhattacharyya AK, Martínez ME, Alberts DS: Association between cyclooxygenase expression and colorectal adenoma characteristics. Cancer Res 63:3891–3893, 2003PubMedGoogle Scholar
  20. 20.
    Bamba H, Ota S, Kato A, Adachi, A, Itoyama S, Matsuzaki F: High expression of cyclooxygenase-2 in macrophages of human colonic adenoma. Int J Cancer 83:470–475, 1999CrossRefGoogle Scholar
  21. 21.
    Yamauchi T, Watanabe M, Kubota T, Hasegawa H, Yoshiyuki I, Endo T, Kabeshima Y, Yorozuya K, Yamamoto K, Mukai M, Kitajima M: Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. Dis Colon Rectum 45:98–103, 2002CrossRefGoogle Scholar
  22. 22.
    Garewal H, Ramsey L, Fass R, Hart NK, Payne CM, Berstein H, Bernstein C: Perils of immunohistochemistry. Dig Dis Sci 48:197–202, 2003CrossRefGoogle Scholar
  23. 23.
    Ohno S, Suzuki N, Ohno Y, Inagawa H, Soma G-I, Inoue M: Tumor-associated macrophages: Foe or accomplice of tumors? Anticancer Res 23:4395–4410, 2003PubMedGoogle Scholar
  24. 24.
    Balkwill F, Mantovani A: Inflammation and cancer: Back to Virchow ? Lancet 357:539–545, 2001CrossRefGoogle Scholar
  25. 25.
    Sica A, Saccani A, Mantovani A: Tumor-associated macrophages: A molecular perspective. Int Immunopharmacol 2:1045–1054, 2002CrossRefGoogle Scholar
  26. 26.
    Ladabaum U, Scheiman JM, Fendrick AM: Potential effect of cyclooxygenase-2-specific inhibitors on the prevention of colorectal cancer: a cost-effectiveness analysis. Am J Med 114:546–554, 2003CrossRefGoogle Scholar
  27. 27.
    Cruz-Correa M, Hylind LM, Romans KE, Booker SV, Giardiello FM: Long-term treatment with sulindac in familial adenomatous polyposis: A prospective cohort study. Gastroenterology 122:641–645, 2002CrossRefGoogle Scholar
  28. 28.
    Rüschoff J, Wallinger S, Dietmaier W, Bocker T, Brockhoff G, Hofstädter F, Fishel R: Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. Proc Natl Acad Sci 95:11301–11306, 1998CrossRefGoogle Scholar
  29. 29.
    Azumaya M, Kobayashi M, Ajioka Y, Honma T, Suzuki Y, Takeuchi M, Narisawa R, Asakura H: Size-dependent expression of cyclooxygenase-2 in sporadic colorectal adenomas relative to adenomas in patients with familial adenomatous polyposis. Pathology Int 52:272–276, 2002CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Eli Brazowski
    • 1
  • Faina Misonzhnick-Bedny
    • 1
  • Paul Rozen
    • 2
    • 3
    Email author
  1. 1.Department of PathologyTel Aviv Medical CenterIsrael
  2. 2.Department of GastroenterologyTel Aviv Medical CenterTel AvivIsrael
  3. 3.Tel Aviv UniversityTel AvivIsrael

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