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Expression of β-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases
  1. V Hervieu1,*,
  2. F Lepinasse1,*,
  3. G Gouysse1,
  4. O Guillaud1,3,
  5. C Barel3,
  6. M-L Chambonniere1,
  7. P-P Bringuier1,
  8. G Poncet1,3,
  9. C Lombard-Bohas3,
  10. C Partensky3,
  11. J-A Chayvialle1,
  12. J-Y Scoazec1,2
  1. 1INSERM, Unité 45, IFR62, Faculté Laennec, Lyon, France
  2. 2Service Central d’Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
  3. 3Fédération des Spécialités Digestives, Lyon, France
  1. Correspondence to:
 Dr J-Y Scoazec
 Anatomie Pathologique, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69437 Lyon cedex 03, France; jean-yves.scoazec{at}chu-lyon.fr

Abstract

Aims: To clarify the role of β-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of β-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in β-catenin expression.

Methods: 229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of β-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene.

Results: The distribution of immunoreactive β-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of β-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months.

Conclusions: Immunohistochemically detectable nuclear accumulation of β-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in β-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.

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Footnotes

  • Published Online First 26 May 2006

  • * Both these authors contributed equally to the work and must therefore be considered as first coauthors.

  • Competing interests: None declared.

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