Digestive Diseases and Sciences

, Volume 53, Issue 3, pp 723–729 | Cite as

An Anti-adenoma Antibody, Adnab-9, May Reflect the Risk for Neoplastic Progression in Familial Hamartomatous Polyposis Syndromes

  • Martin Tobi
  • Michael Kam
  • Nadeem Ullah
  • Kashif Qureshi
  • Violeta Yordanova
  • James Hatfield
  • Suzanne E. G. Fligiel
  • Paula Sochacki
  • Thomas McGarrity
  • Carolyn Cole
  • Michael Lawson
  • Russell Jacoby
Original Paper


Patients with the hamartomatous polyposis Peutz-Jeghers and familial juvenile polyposis syndromes are predisposed to colorectal cancer but lack early genetic alterations found in adenomatous premalignant lesions. We studied hamartomatous polyps for the expression of an early preneoplastic colorectal neoplasia risk marker also found in familial adenomatous polyposis patients. Retrospective, genetic, and hospital archival tissue immunohistochemistry using Adnab-9, a premalignant marker often found in Paneth-like cells (PCs), was performed on sections of polyps from eight patients with Peutz-Jeghers syndrome, eight patients with familial juvenile polyposis, and 36 hyperplastic polyp control sections. Anti-α-defensin 5 (AD5), a universal PC marker, was also used to label a subgroup of sections. Hamartomatous polyposis patients also underwent specific genetic analysis. Eighty-nine percent of Peutz-Jeghers syndrome polyps labeled with Adnab-9 compared with 63% for AD5; 88% of familial juvenile polyposis sections also labeled with Adnab-9. Of the 36 hyperplastic polyp sections, only four (11%) labeled with Adnab-9 and one (3%) with AD5. Adnab-9 labeling of PCs in the epithelial elements of hamartomatous colonic lesions of hereditary hamartomatous syndrome patients reflects the predisposition to colorectal cancer, further justifying early intervention strategies.


Adnab-9 Peutz-Jeghers syndrome Familial juvenile polyposis Anti-α-defensin 5 Paneth-like cells 



Adenomatous polyposis coli


Colorectal cancer




Hereditary familial juvenile polyposis syndrome


Inflammatory bowel disease


Optical densitometry


Peutz-Jeghers syndrome



The authors would like to express their gratitude to Susan Katz, BA, for assistance with specimen collection. The work was supported in part by a Department of Veterans Affairs (VAMC) grant awarded to Dr. Martin Tobi, a Kaiser Permanente Research Foundation grant to Dr. Michael Lawson, and a VAMC Merit Review Grant to Dr. Russell Jacoby. This paper is dedicated to the memory of Irwin Stein.


  1. 1.
    Howe JR, Mitros FA, Summers RW (1998) The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol 5:751–756PubMedCrossRefGoogle Scholar
  2. 2.
    Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJA, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD (1987) Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl Med 316:1511–1513CrossRefGoogle Scholar
  3. 3.
    Jacoby RF, Schlack S, Cole CE et al (1997) A juvenile polyposis tumor suppressor locus at 10q22 is deleted from nonepithelial cells in the lamina propria. Gastroenterology 112:1398–1403PubMedCrossRefGoogle Scholar
  4. 4.
    Hahn SA, Schutte M, Hoque AT et al (1996) DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271:350–353PubMedCrossRefGoogle Scholar
  5. 5.
    Scott RJ, Crooks R, Meldrum CJ et al (2002) Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients. Clin Genet 62:282–287PubMedCrossRefGoogle Scholar
  6. 6.
    Trojan J, Brieger A, Raedle J et al (1999) Peutz-Jeghers syndrome: molecular analysis of a three-generation kindred with a novel defect in the serine threonine kinase gene STK11. Am J Gastroenterol 94:257–261PubMedCrossRefGoogle Scholar
  7. 7.
    Tobi M, Kaila V, Hassan N et al (1999) Monoclonal antibody Adnab-9 defines a preneoplastic marker in epithelium at risk for adenocarcinoma of the small intestine. Hum Pathol 30:467–473PubMedCrossRefGoogle Scholar
  8. 8.
    Tobi M, Maliakkal BJ, Alousi MA et al (1992) Cellular distribution of a colonic adenoma-associated antigen as defined by monoclonal antibody Adnab-9. Scand J Gastroenterol 27:737–742PubMedCrossRefGoogle Scholar
  9. 9.
    Sheikh R, Min B, Yasmeen S et al (2003) Comparison of Ki-67, Adnab-9, p53 immunohistochemical staining, and ploidy with clinical and histological features of severely dysplastic colorectal adenomas. Dig Dis Sci 48:223–229PubMedCrossRefGoogle Scholar
  10. 10.
    Tobi M (1999) Polyps as Biomarkers for colorectal Neoplasia. Front Biosci 4:D329–D338. http://www.bioscience.org/1999/v4/d/tobi/fulltext.htm
  11. 11.
    Cunliffe RN, Rose FR, Keyte J, Abberley L, Chan WC, Mahida YR (2001) Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut 48:176–185PubMedCrossRefGoogle Scholar
  12. 12.
    Wehkamp J, Schwind B, Herrlinger KR, Baxmann S, Schmidt K, Duchrow M, Wohlschlager C, Feller AC, Stange EF, Fellermann K (2002) Innate immunity and colonic inflammation: enhanced expression of epithelial alpha-defensin. Dig Dis Sci 47:1349–1355PubMedCrossRefGoogle Scholar
  13. 13.
    Tobi M, Elitsur Y, Moyer MP et al (1993) Mucosal origin and shedding of an early colonic tumor marker defined by Adnab-9 monoclonal antibody. Scand J Gastroenterol 28:1025–1034PubMedCrossRefGoogle Scholar
  14. 14.
    McGarrity TJ, Kulin HE, Zaino RJ (2000) Peutz-Jeghers Syndrome. Am J Gastroenterol 95:596–605PubMedCrossRefGoogle Scholar
  15. 15.
    Hsu SM, Raine L, Fanger V (1981) Use of Avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PA) procedures. J Histochem 21:577–580Google Scholar
  16. 16.
    Ullah N, Qureshi K, Hatfield J, Sochacki P, David D, Albataineh H, Mejia L, Kenkre C, Lawson M, Tobi M (2004) Small early tubular adenomas and mixed colonic polyps found on screening flexible sigmoidoscopy do not predict proximal neoplasia in males. Clin Gastroenterol Hepatol 2:246–251PubMedCrossRefGoogle Scholar
  17. 17.
    Ullah N, Qureshi K, Yordanova V et al (2005) Differential labeling by monoclonal antibodies Adnab-9 and anti-α-Defensin 5 based on the distribution and adenomatous tissue content of colonic polyps. Dig Dis Sci 50(4):701–713CrossRefGoogle Scholar
  18. 18.
    Jiang C-Y, Esufali S, Berk T et al (1999) STK11/LKB1 germline mutations are not identified in most Peutz-Jeghers syndrome patients. Clin Genet 56:136–141PubMedCrossRefGoogle Scholar
  19. 19.
    Tobi M, Hatfield J, Adsay V et al (2001) Prognostic significance of the labeling of Adnab-9, in pancreatic intraductal papillary mucinous neoplasms. Int J Pancreatol 29:139–148Google Scholar
  20. 20.
    Tobi M, Prabhu S, Gage R, Orr T, Lawson MJ (2002) Colorectal cancer risk: the impact of evidence of a field effect of carcinogenesis on blinded diagnosis using an anti-adenoma antibody test performed on colonoscopic effluent. Dig Dis Sci 47:317–321PubMedCrossRefGoogle Scholar
  21. 21.
    McGarrity TJ, Peiffer LP, Amos CI et al (2003) Overexpression of cyclooxygenase 2 in hamartomatous polyps of Peutz-Jeghers syndrome. Am J Gastroenterol 98:671–678PubMedCrossRefGoogle Scholar
  22. 22.
    Udd L, Katajisto P, Rossi DJ et al (2004) Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2. Gastroenterology 127:1030–1037PubMedCrossRefGoogle Scholar
  23. 23.
    Qiao SX, Yuan M, Liu YL et al (2003) Detection of gastric cancer and premalignant lesions by a novel marker GP87 using monoclonal antibody Adnab-9. Cancer Epidemiol Biomarkers Prev 12:1095–1099PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Martin Tobi
    • 1
    • 2
  • Michael Kam
    • 1
  • Nadeem Ullah
    • 1
  • Kashif Qureshi
    • 1
  • Violeta Yordanova
    • 1
  • James Hatfield
    • 1
  • Suzanne E. G. Fligiel
    • 1
  • Paula Sochacki
    • 1
  • Thomas McGarrity
    • 3
  • Carolyn Cole
    • 4
  • Michael Lawson
    • 5
  • Russell Jacoby
    • 4
  1. 1.John D. Dingell VAMC Departments of Medicine, Gastroenterology and PathologyWayne State University School of MedicineDetroitUSA
  2. 2.Section Gastroenterology MED III/GIPhiladelphia VAMCPhiladelphiaUSA
  3. 3.Department of Medicine, The Milton S. Hershey Medical CenterThe Pennsylvania State University College of MedicineHersheyUSA
  4. 4.Wm. S. Middelton Memorial VAMCUniversity Wisconsin Comprehensive Cancer CenterMadisonUSA
  5. 5.Kaiser Permanente Medical GroupSacramentoUSA

Personalised recommendations