703P - Small bowel adenocarcinoma phenotype according to the primary localisation

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Gastrointestinal Cancers
Pathology/Molecular Biology
Presenter Thomas Aparicio
Authors T. Aparicio1, M. Svrcek2, A. Laforest3, A. Zaanan4, P. Afchain5, E. Mitry6, J. Taieb4, F. Di Fiore7, J. Gornet8, P. Laurent-Puig3
  • 1Hopital Avicenne, 93009 - Bobigny CEDEX/FR
  • 2Pathology, Hôpital Saint Antoine, AP-HP, Paris/FR
  • 3Umr-s775, Université Paris Descartes, Paris/FR
  • 4Gastroenterology, Hôpital Européen Georges Pompidou, APHP, Paris/FR
  • 5Oncology, Hôpital Saint Antoine, AP-HP, Paris/FR
  • 6Oncology, Institut Curie, Paris/FR
  • 7Digestive Oncology Unit, C.H.U. Charles Nicolle, FR-76000 - Rouen/FR
  • 8Gastroenterology, Hôpital Saint Louis, Paris/FR

Abstract

Background

Small bowel adenocarcinoma (SBA) is a rare tumor with poor prognosis. Data about molecular biology on SBA carcinogenesis are lacking.

Methods

We characterised a number of candidate oncogenic pathways and the immunophenotype according to the primary localisation of patients with SBA treated in 11 centers between 1996 and 2008. Tissue microarrays were constructed from tumour samples and DNAs were extracted from formalin fixed paraffin embedded samples. HER2, b catenin, TP53 and mismatch repair (MMR) protein expression were assessed by immunohistochemistry. Overexpression of TP53 was defined as more than 50% of cells with nuclear staining. Abnormal expression of b catenin was defined as a nuclear staining. KRAS mutation was investigated. Patients were enrolled in the study at all stage of the disease.

Results

Samples from 63 patients were obtained, ampullary tumours were excluded. The median age was 58 years. Tumour stages were I-II n = 19 (30%), III n = 22 (35%), IV n = 20 (32%) and undefined n = 2 (3%). A HER2 surexpression (3+) was observed in 2/51 (3.9%) cases both in ileum. Overexpression of TP53 was observed in 23/53 (43%). Abnormal expression of b catenin was observed in 11/52 (21%) cases. A loss of MMR proteins occurred in 7/55 (13%) cases (3 MLH1, 2 MSH2, 2 MSH6), none was stage IV. A KRAS mutation was observed in 19/48 (40%) cases that involved codon 12 in 13 (68%) cases or G > A transition in 16 (84%). Tumours with KRAS mutation were stage IV in 31% of the cases. Survival analysis will be available at the meeting.

Conclusion

This large study suggests that molecular phenotype of SBA is close to colon phenotype with low level of HER 2 surexpression and high level of KRAS mutation. Ileum tumours seem to have a different phenotype than proximal tumours.

Duodenum n = 32 (51%) Jejunum n = 18 (28%) Ileum n = 13 (21%)
Stage IV n = 20 9 (45%) 6 (30%) 5 (25%)
HER2 surexpression n = 2 0 (0%) 0 (0%) 2 (100%)
TP53 overexpression n = 23 12 (52%) 6 (26%) 5 (22%)
Abnormal b catenin n = 11 4 (36%) 2 (18%) 5 (45%)
Abnormal MMR n = 7 3 (43%) 4 (57%) 0 (0%)
KRAS mutation n = 19 11 (58%) 6 (32%) 2 (10%)
Disclosure

All authors have declared no conflicts of interest.