Skip to main content

Advertisement

Log in

The monoclonal anti-BCL10 antibody (clone 331.1) is a sensitive and specific marker of pancreatic acinar cell carcinoma and pancreatic metaplasia

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Acinar cell carcinoma (ACC) is a rare pancreatic cancer which may be difficult to distinguish from other solid nonadenocarcinoma tumors. The diagnosis depends on the demonstration of acinar differentiation, obtained with antibodies recognizing various pancreatic enzymes that, although specific, show different sensitivity. The C-terminal portion of the BCL10 protein shows homology with carboxyl ester hydrolase (CEH), an enzyme produced by pancreatic acinar cells. We investigated the usefulness of a C-terminal BCL10 monoclonal antibody in the diagnosis of ACCs. We examined normal pancreases and different pancreatic tumors including ACCs, mixed acinar–endocrine carcinomas, ductal adenocarcinomas, mucinous, serous, solid pseudopapillary, and endocrine neoplasms. In addition, various normal tissues and cases of pancreatic metaplasia of the gastroesophageal mucosa, cases of ectopic pancreas, gastrointestinal endocrine tumors, salivary and breast acinic cell carcinomas, gastric adenocarcinomas with and without acinar differentiation, and hepatocellular carcinomas were studied. BCL10 immunoreactivity paralleled that of CEH and was restricted to acinar cells of normal and ectopic pancreas, of pancreatic metaplasia, and of ACCs. The anti-BCL10 antibody was more sensitive in detecting ACCs and pancreatic metaplasia than antibodies directed against other pancreatic enzymes. We suggest using BCL10 antibody for diagnosing pancreatic tumors and whenever an acinar differentiation is suspected in gastrointestinal neoplastic and metaplastic lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Hruban RH, Pitman MB, Klimstra DS (2007) Acinar neoplasms. In: Silverberg SG, Sobin LH (eds) Atlas of tumor pathology, series 4. Tumors of the pancreas. American Registry of Pathology, Washington, DC, pp 191–218

    Google Scholar 

  2. Lack EE (2003) Acinar cell carcinoma. In: Lack EE (ed) Pathology of the pancreas, gallbladder, extrahepatic biliary tract, and ampullary region. Oxford University Press, New York, pp 307–317

    Google Scholar 

  3. Klöppel G (2000) Mixed exocrine–endocrine tumors of the pancreas. Semin Diagn Pathol 17:104–108

    PubMed  Google Scholar 

  4. Ohike N, Kosmahl M, Klöppel G (2004) Mixed acinar–endocrine carcinoma of the pancreas: a clinico-pathological study and comparison with acinar cell carcinoma. Virchows Arch 445:231–235

    Article  PubMed  Google Scholar 

  5. Volante M, Righi L, Asioli S et al (2007) Goblet cell carcinoids and other mixed neuroendocrine/nonneuroendocrine neoplasms. Virchows Arch 451(suppl 1):S61–S69

    Article  PubMed  Google Scholar 

  6. Holen KD, Klimstra DS, Hummer A et al (2002) Clinical characteristics and outcomes from an institutional series of acinar cell carcinoma of the pancreas and related tumors. J Clin Oncol 20:4673–4678

    Article  PubMed  Google Scholar 

  7. Morohoshi T, Kanda M, Horie A et al (1987) Immunocytochemical markers of uncommon pancreatic tumors. Acinar cell carcinoma, pancreatoblastoma, and solid cystic (papillary-cystic) tumor. Cancer 59:739–747

    Article  PubMed  CAS  Google Scholar 

  8. Solcia E, Capella C, Klöppel G (1997) Acinar cell carcinoma. In: Rosai J, Sobin LH (eds) Atlas of tumor pathology: tumors of the pancreas. Armed Forces Institute of Pathology, Washington, DC, pp 103–112

    Google Scholar 

  9. Carrère J, Figarella-Branger D, Senegas-Balas F et al (1992) Immunohistochemical study of secretory proteins in the developing human exocrine pancreas. Differentiation 51:55–60

    Article  PubMed  Google Scholar 

  10. Lombardo D, Guy O, Figarella C (1978) Purification and characterization of carboxyl ester hydrolase from human pancreatic juice. Biochim Biophys Acta 527:142–149

    PubMed  CAS  Google Scholar 

  11. Rinderknecht H (1993) Pancreatic secretory enzymes. In: Go VLW, DiMagno EP, Gardner JD et al (eds) The pancreas: biology, pathobiology, and disease, 2nd edn. Raven, New York, pp 219–251

    Google Scholar 

  12. Nilsson J Blackberg L, Carlsson P et al (1990) cDNA cloning of human-milk bile-salt-stimulated lipase and evidence for its identity to pancreatic carboxylic ester hydrolase. Eur J Biochem 192:543–550

    Article  Google Scholar 

  13. Christie DL, Cleverly DR, O’Connor CJ (1991) Human milk bile-salt stimulated lipase. Sequence similarity with rat lysophospholipase and homology with the active site region of cholinesterases. FEBS Lett 278:190–194

    Article  PubMed  CAS  Google Scholar 

  14. Wang CS (1988) Purification of carboxyl ester lipase from human pancreas and the amino acid sequence of the N-terminal region. Biochem Biophys Res Commun 155:950–955

    Article  PubMed  CAS  Google Scholar 

  15. Bernback S, Blackberg L, Hernell O (1990) The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase. J Clin Invest 85:1221–1226

    Article  PubMed  CAS  Google Scholar 

  16. Brodt-Eppley J, White P, Jenkins S et al (1995) Plasma cholesterol esterase level is a determinant for an atherogenic lipoprotein profile in normolipidemic human subjects. Biochem Biophys Acta 1272:69–72

    PubMed  Google Scholar 

  17. Li F, Hui DY (1998) Synthesis and secretion of the pancreatic-type carboxyl ester lipase by human endothelial cells. Biochem J 329:675–679

    PubMed  CAS  Google Scholar 

  18. Willis TG, Jadayel DM, Du MQ et al (1999) BCL10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 96:35–45

    Article  PubMed  CAS  Google Scholar 

  19. Basturk O, Zamboni G, Klimstra DS et al (2007) Intraductal and papillary variants of acinar cell carcinomas. A new addition to the challenging differential diagnosis of intraductal neoplasms. Am J Surg Pathol 31:363–370

    Article  PubMed  Google Scholar 

  20. La Rosa S, Rigoli E, Uccella S et al (2004) CDX2 as a marker of intestinal EC-cells and related well-differentiated endocrine tumors. Virchows Arch 445:248–254

    Article  PubMed  CAS  Google Scholar 

  21. Qiu J, Hendrixson DR, Baker EN et al (1998) Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae. Proc Natl Acad Sci U S A 95:12641–12646

    Article  PubMed  CAS  Google Scholar 

  22. Henley JD, Geary WA, Jackson CL et al (1997) Dedifferentiated acinic cell carcinoma of the parotid gland: a distinct rarely described entity. Hum Pathol 28:869–873

    Article  PubMed  CAS  Google Scholar 

  23. Kuopio T, Ekfors TO, NIkkanen V et al (1995) Acinar cell carcinoma of the pancreas. Report of three cases. APMIS 103:69–78

    Article  PubMed  CAS  Google Scholar 

  24. Ordonez NG (2001) Pancreatic acinar cell carcinoma. Adv Anat Pathol 8:144–159

    Article  PubMed  CAS  Google Scholar 

  25. Klimstra DS, Heffess CS, Oertel JE et al (1992) Acinar cell carcinoma of the pancreas. A clinico-pathologic study of 28 cases. Am J Pathol 16:815–837

    Article  CAS  Google Scholar 

  26. Hoorens A, Lemoine NR, McLellan E et al (1993) Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation. Am J Pathol 143:685–698

    PubMed  CAS  Google Scholar 

  27. Reuss R, Aberle S, Klingel K et al (2006) The expression of the carboxyl ester lipase gene in pancreas and pancreatic adenocarcinomas. Int J Oncol 29:649–654

    PubMed  CAS  Google Scholar 

  28. Aho HJ, Sternby B, Kallajoki M et al (1989) Carboxyl ester lipase in human tissues and acute pancreatitis. Int J Pancreatol 5:123–134

    PubMed  CAS  Google Scholar 

  29. Nilsson J, Hellquist M, Bjursell G (1993) The human carboxyl ester lipase-like (CELL) gene is ubiquitously expressed and contains a hypervariable region. Genomics 17:416–422

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the University of Insubria, Varese. Silvia Marchet is the recipient of a fellowship from the “Varese per l’Oncologia” Association. The authors thank Anna and baby Riccardo La Rosa for providing samples of human milk and Dr. Luigi Terracciano (Institute of Pathology, University Hospital of Basel, Switzerland) for preparing the microarray slides.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefano La Rosa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

La Rosa, S., Franzi, F., Marchet, S. et al. The monoclonal anti-BCL10 antibody (clone 331.1) is a sensitive and specific marker of pancreatic acinar cell carcinoma and pancreatic metaplasia. Virchows Arch 454, 133–142 (2009). https://doi.org/10.1007/s00428-008-0710-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-008-0710-x

Keywords

Navigation