Open Access Short report

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

Massimo Pancione1, Andrea Remo2, Lina Sabatino1, Caterina Zanella2, Carolina Votino1, Alessandra Fucci1, Arturo Di Blasi3, Giovanni Lepore3, Bruno Daniele3, Francesca Fenizia4, Enrico Molinari5, Nicola Normanno4, Erminia Manfrin6, Roberto Vendraminelli2 and Vittorio Colantuoni1*

Author Affiliations

1 Department of Biological, Geological and Environmental Sciences, University of Sannio, Via Port’Arsa, Benevento, 11 82100, Italy

2 Department of Pathology “Mater Salutis” Hospital, ULSS21, Legnago, Verona, Italy

3 Departments of Oncology and Pathology, Azienda Ospedaliera “G. Rummo”, Benevento, 82100, Italy

4 Center for Oncology Research, Pharmacogenomic Laboratory, Mercogliano, Avellino, 83013, Italy

5 Department of Surgery “Mater Salutis” Hospital, ULSS21, Legnago, Verona, Italy

6 Department of Pathology “G.B. Rossi” Hospital, University of Verona, Verona, Italy

For all author emails, please log on.

Diagnostic Pathology 2013, 8:31  doi:10.1186/1746-1596-8-31

Published: 20 February 2013

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.

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 webcite

Keywords:
Rhabdoid Colorectal Tumor, RCT; CpG island methylator phenotype, CIMP; Serrated pathway