Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine.
BACKGROUND
Despite having a dramatically larger surface area than the large intestine, the small intestine is an infrequent site for the development of adenocarcinoma. To better understand the molecular abnormalities in small bowel adenocarcinoma (SBA), we characterised a number of candidate oncogenic pathways and the immunophenotype of this rare cancer.


METHODS
Tissue microarrays were constructed from tumour samples from 54 patients with all stages of the disease. Immunohistochemistry and microsatellite instability (MSI) testing were conducted.


RESULTS
The profile of cytokeratin 20 and 7 coexpression was variable, but expression of caudal type homeobox transcription factor 2 (CDX2) was present in 70% of cases. In this young population (median age 54 years), loss of mismatch repair (MMR) proteins occurred in 35% of patients, with confirmed MSI in 100% of tested cases. Expression of vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor receptor (EGFR) was common, occurring in 96 and 71% of patients, respectively. Only one case showed HER2 expression and none showed loss of phosphatase and tensin homologue mutated on chromosome 10 (PTEN).


CONCLUSIONS
These results suggest that alterations in DNA MMR pathways are common in SBAs, similar to what is observed in large bowel adenocarcinomas. Furthermore, the high percentage of tumours expressing both EGFR and VEGF suggests that patients with this rare cancer may benefit from therapeutic strategies targeting EGFR and VEGF receptor (VEGFR).
Overman
M J
MJ
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. moverman@mdanderson.org
Pozadzides
J
J
Kopetz
S
S
Wen
S
S
Abbruzzese
J L
JL
Wolff
R A
RA
Wang
H
H
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D000071616:CDX2 Transcription Factor; D053843:DNA Mismatch Repair / Q000235:genetics; D004379:Duodenal Neoplasms / Q000235:genetics* / Q000276:immunology; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007078:Ileal Neoplasms / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D007580:Jejunal Neoplasms / Q000235:genetics / Q000276:immunology; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000235:genetics
D000071616:CDX2 Transcription Factor; D066246:ErbB Receptors; D018398:Homeodomain Proteins; D007633:Keratins; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; C491270:CDX2 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human