title: Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study.
abstract: BACKGROUND
  Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking.
  
  
  METHODS
  Expression of HER2, β-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated.
  
  
  RESULTS
  We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of β-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS.
  
  
  CONCLUSIONS
  This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.
authors.affiliation: Gastroenterology and Digestive Oncology, APHP, Hôpitaux Universitaires de Seine Saint Denis, Avicenne Hospital, University Paris 13, Paris Sorbonne Cité, 125 rue de Stalingrad, Bobigny 93000, France.
authors.forename: T
authors.initials: T
authors.lastname: Aparicio
authors.forename: M
authors.initials: M
authors.lastname: Svrcek
authors.forename: A
authors.initials: A
authors.lastname: Zaanan
authors.forename: E
authors.initials: E
authors.lastname: Beohou
authors.forename: A
authors.initials: A
authors.lastname: Laforest
authors.forename: P
authors.initials: P
authors.lastname: Afchain
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mitry
authors.forename: J
authors.initials: J
authors.lastname: Taieb
authors.forename: F
authors.initials: F
authors.lastname: Di Fiore
authors.forename: J-M
authors.initials: JM
authors.lastname: Gornet
authors.forename: A
authors.initials: A
authors.lastname: Thirot-Bidault
authors.forename: I
authors.initials: I
authors.lastname: Sobhani
authors.forename: D
authors.initials: D
authors.lastname: Malka
authors.forename: T
authors.initials: T
authors.lastname: Lecomte
authors.forename: C
authors.initials: C
authors.lastname: Locher
authors.forename: F
authors.initials: F
authors.lastname: Bonnetain
authors.forename: P
authors.initials: P
authors.lastname: Laurent-Puig
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis