Right-sided rhabdoid colorectal tumors might be related to the Serrated Pathway

Autor: Caterina Zanella, Roberto Vendraminelli, Alessandra Fucci, Arturo Di Blasi, Massimo Pancione, Andrea Remo, Erminia Manfrin, Lina Sabatino, Francesca Fenizia, Nicola Normanno, Bruno Daniele, Vittorio Colantuoni, Giovanni Lepore, Carolina Votino, Enrico Molinari
Rok vydání: 2013
Předmět:
Pathology
Time Factors
Chromosomes
Human
Pair 22
DNA Mutational Analysis
Polymerase Chain Reaction
Epigenesis
Genetic
Pathogenesis
Fatal Outcome
Intestinal mucosa
Neoplasm
Intestinal Mucosa
SMARCB1
In Situ Hybridization
Fluorescence
Gene Rearrangement
Paraffin Embedding
General Medicine
Immunohistochemistry
Phenotype
Treatment Outcome
Disease Progression
Female
Microsatellite Instability
Colorectal Neoplasms
RCT
Signal Transduction
Adenoma
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Histology
Short Report
CpG island methylator phenotype
Biology
Pathology and Forensic Medicine
Biomarkers
Tumor
medicine
Humans
Genetic Predisposition to Disease
Rhabdoid Tumor
Aged
CIMP
Rhabdoid Colorectal Tumor
Serrated pathway
Microsatellite instability
Gene rearrangement
DNA Methylation
medicine.disease
CpG island methylator phenotype
CIMP
Rhabdoid Colorectal Tumor
RCT
Mutation
CpG Islands
Differential diagnosis
Zdroj: Diagnostic Pathology
ISSN: 1746-1596
DOI: 10.1186/1746-1596-8-31
Popis: 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. Materials and 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. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1641385210804556
Databáze: OpenAIRE
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