BACKGROUND: Primary adenocarcinomas of the small intestine are rare, and the genetic mechanisms involved in their carcinogenesis remain unclear. AIM: To examine the expression of candidate proteins in small intestinal adenocarcinomas by immunohistochemistry performed on tissue microarrays (TMAs). METHODS: Twenty seven primary sporadic small intestinal adenocarcinomas were analysed. The TMA technique was validated by comparing immunohistochemical labelling of hMLH1 and hMSH2 on TMAs and the tissue sections they derived from. The expression of Smad4, hMSH6, beta catenin, and p53 was investigated and results compared with those obtained in 14 malignant ampullary tumours. RESULTS: TMA technology with threefold redundancy adequately represented the immunohistochemical pattern of small intestinal adenocarcinomas. Loss of hMLH1 expression, but not hMSH2 or hMSH6, was seen in two of 27 small intestinal adenocarcinomas. All ampullary tumours showed nuclear staining for hMSH2 and hMSH6. One case showed lack of immunostaining for hMLH1. Smad4 expression was absent in five small intestinal adenocarcinomas and two ampullary tumours. Overexpression of p53 was detected in the nuclei of 14 of the 27 small intestinal adenocarcinomas, and five of the 14 ampullary tumours. Nuclear or cytoplasmic expression of beta catenin was present in all specimens. CONCLUSION: Inactivation of the SMAD4/DPC4 gene seems to be involved in small intestinal adenocarcinoma tumorigenesis. Overexpression of p53 and abnormal expression of beta catenin are two common events, unlike the loss of expression of the DNA mismatch repair proteins (hMLH1, hMSH2, and hMSH6). The carcinogenetic process appears to be similar in small intestinal adenocarcinomas and malignant ampullary tumours.
BACKGROUND: Primary adenocarcinomas of the small intestine are rare, and the genetic mechanisms involved in their carcinogenesis remain unclear. AIM: To examine the expression of candidate proteins in small intestinal adenocarcinomas by immunohistochemistry performed on tissue microarrays (TMAs). METHODS: Twenty seven primary sporadic small intestinal adenocarcinomas were analysed. The TMA technique was validated by comparing immunohistochemical labelling of hMLH1 and hMSH2 on TMAs and the tissue sections they derived from. The expression of Smad4, hMSH6, beta catenin, and p53 was investigated and results compared with those obtained in 14 malignant ampullary tumours. RESULTS: TMA technology with threefold redundancy adequately represented the immunohistochemical pattern of small intestinal adenocarcinomas. Loss of hMLH1 expression, but not hMSH2 or hMSH6, was seen in two of 27 small intestinal adenocarcinomas. All ampullary tumours showed nuclear staining for hMSH2 and hMSH6. One case showed lack of immunostaining for hMLH1. Smad4 expression was absent in five small intestinal adenocarcinomas and two ampullary tumours. Overexpression of p53 was detected in the nuclei of 14 of the 27 small intestinal adenocarcinomas, and five of the 14 ampullary tumours. Nuclear or cytoplasmic expression of beta catenin was present in all specimens. CONCLUSION: Inactivation of the SMAD4/DPC4 gene seems to be involved in small intestinal adenocarcinoma tumorigenesis. Overexpression of p53 and abnormal expression of beta catenin are two common events, unlike the loss of expression of the DNA mismatch repair proteins (hMLH1, hMSH2, and hMSH6). The carcinogenetic process appears to be similar in small intestinal adenocarcinomas and malignant ampullary tumours.
Authors: N Arber; H Hibshoosh; W Yasui; A I Neugut; A Hibshoosh; Y Yao; A Sgambato; H Yamamoto; I Shapira; D Rosenman; I Fabian; I B Weinstein; E Tahara; P R Holt Journal: Cancer Epidemiol Biomarkers Prev Date: 1999-12 Impact factor: 4.254
Authors: J M D Wheeler; B F Warren; N J McC Mortensen; H C Kim; S C Biddolph; G Elia; N E Beck; G T Williams; N A Shepherd; A C Bateman; W F Bodmer Journal: Gut Date: 2002-02 Impact factor: 23.059
Authors: K L Woodford-Richens; A J Rowan; P Gorman; S Halford; D C Bicknell; H S Wasan; R R Roylance; W F Bodmer; I P Tomlinson Journal: Proc Natl Acad Sci U S A Date: 2001-07-31 Impact factor: 11.205
Authors: L Cawkwell; F Sutherland; H Murgatroyd; P Jarvis; S Gray; D Cross; N Shepherd; D Day; P Quirke Journal: Gut Date: 2000-03 Impact factor: 23.059
Authors: R E Wilentz; C A Iacobuzio-Donahue; P Argani; D M McCarthy; J L Parsons; C J Yeo; S E Kern; R H Hruban Journal: Cancer Res Date: 2000-04-01 Impact factor: 12.701
Authors: P S Moore; S Orlandini; G Zamboni; P Capelli; G Rigaud; M Falconi; C Bassi; N R Lemoine; A Scarpa Journal: Br J Cancer Date: 2001-01 Impact factor: 7.640
Authors: Heather Hampel; Wendy L Frankel; Edward Martin; Mark Arnold; Karamjit Khanduja; Philip Kuebler; Mark Clendenning; Kaisa Sotamaa; Thomas Prior; Judith A Westman; Jenny Panescu; Dan Fix; Janet Lockman; Jennifer LaJeunesse; Ilene Comeras; Albert de la Chapelle Journal: J Clin Oncol Date: 2008-09-22 Impact factor: 44.544
Authors: T Aparicio; M Svrcek; A Zaanan; E Beohou; A Laforest; P Afchain; Emmanuel Mitry; J Taieb; F Di Fiore; J-M Gornet; A Thirot-Bidault; I Sobhani; D Malka; T Lecomte; C Locher; F Bonnetain; P Laurent-Puig Journal: Br J Cancer Date: 2013-11-05 Impact factor: 7.640