title: Right-sided rhabdoid colorectal tumors might be related to the serrated pathway.
abstract: BACKGROUND
  Rhabdoid colorectal tumor (RCT) is a rare, highly aggressive neoplasm recurrent in elderly patients, commonly at the caecum. The molecular mechanisms underlying RCT pathogenesis remain poorly elucidated. The differential diagnosis is with the malignant rhabdoid tumors of infancy characterized by genetic inactivation of SMARCB1 (INI1) or deletions of chromosome 22q12 locus.
  
  
  METHODS
  To shed light on RCT pathogenesis, we investigated genetic and epigenetic alterations in two cases of pure and composite RCT and compared them with the profiles of matched adenomas and normal mucosa. Immunohistochemical analysis, FISH, methylation specific PCR and DNA sequencing analysis were performed on paraffin-embedded tissues.
  
  
  RESULTS
  Loss of epithelial markers, (CK20, CDX2 and E-cadherin) and intense vimentin expression was observed in RCTs but neither in the normal mucosa or adenomas. INI1 expression was detected in normal mucosa, adenomas and retained in pure RCT, while it was undetected in composite RCT. Rearrangement of the 22q12 locus was found only in pure RCT. The APC/β-catenin pathway was not altered, while MLH1 immunostaining was negative in RCTs and positive in adenomas and normal mucosa. These expression profiles were associated with V600E BRAF mutation, a progressive accumulation of promoter methylation at specific CIMP loci and additional genes from the normal mucosa to tubular adenoma and RCT.
  
  
  CONCLUSIONS
  Right-sided RCT could be characterized by epigenetic events and molecular features likely similar to those occurring in the serrated pathway and associated with epithelial-mesenchymal transition. These extremely rare tumors may benefit from the use of new biological molecules specific for colorectal carcinoma.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1641385210804556.
authors: Department of Biological, Geological and Environmental Sciences, University of Sannio, Benevento, Italy.
authors: Massimo
authors: M
authors: Pancione
authors: Andrea
authors: A
authors: Remo
authors: Lina
authors: L
authors: Sabatino
authors: Caterina
authors: C
authors: Zanella
authors: Carolina
authors: C
authors: Votino
authors: Alessandra
authors: A
authors: Fucci
authors: Arturo
authors: A
authors: Di Blasi
authors: Giovanni
authors: G
authors: Lepore
authors: Bruno
authors: B
authors: Daniele
authors: Francesca
authors: F
authors: Fenizia
authors: Enrico
authors: E
authors: Molinari
authors: Nicola
authors: N
authors: Normanno
authors: Erminia
authors: E
authors: Manfrin
authors: Roberto
authors: R
authors: Vendraminelli
authors: Vittorio
authors: V
authors: Colantuoni
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018450:Disease Progression; D044127:Epigenesis, Genetic; D017809:Fatal Outcome; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology; D053842:Microsatellite Instability; D009154:Mutation; D016612:Paraffin Embedding; D010641:Phenotype; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf