A novel case of rhabdoid colon carcinoma associated with a positive CpG island methylator phenotype and BRAF mutation

Hum Pathol. 2011 Jul;42(7):1047-52. doi: 10.1016/j.humpath.2010.10.016. Epub 2011 Feb 11.

Abstract

Colon carcinoma with rhabdoid characteristics is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a colon adenocarcinoma with rhabdoid features in a 71-year-old woman, localized to the right colon and associated with local lymph node and liver metastasis. The patient died within 8 months from surgery despite target chemotherapy. The tumor was enriched in cells with a typical rhabdoid-type morphology displaying a marked and diffuse vimentin staining. Cells were also positive for epidermal growth factor receptor (EGFR), p53, Ki67, and β-catenin and negative for cytokeratin 20/cytokeratin 7, E-cadherin, and CDX2. Remarkably, the promoter regions of 4 of 5 specific genes that define the so-called "CpG island methylator phenotype," including mutL homolog 1 (MLH1), were methylated. Consistently, microsatellite instability was detected. A BRAF V600E mutation and no KRAS mutations were identified. Finally, 4 tumor suppressor gene promoters CDH1, CDKN1B, CDKN1C, and MGMT were not methylated. This is the first case of a colorectal carcinoma with rhabdoid features, "CpG island methylator phenotype," high microsatellite instability associated with a BRAF mutation, and patient poorer outcome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • CpG Islands*
  • DNA Methylation*
  • Female
  • Humans
  • Microsatellite Instability
  • Phenotype
  • Proto-Oncogene Proteins B-raf / genetics*
  • Rhabdoid Tumor / genetics*
  • Rhabdoid Tumor / pathology

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf