Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses

Head Neck. 2006 Oct;28(10):909-15. doi: 10.1002/hed.20433.

Abstract

Background: Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses shows microscopic features indistinguishable from colorectal cancer. Our aim was to verify whether the morphologic resemblances mirror genetic profile similarities.

Methods: Twenty consecutive surgically treated ITAC cases, previously investigated for p16(INK4a) and TP53, were investigated for hMLH1, hMSH2, and beta-catenin immunoreactivity, and for adenomatous polyposis coli (APC), K-ras, and BRAF gene mutations.

Results: One case was immunonegative for both hMLH1 and hMSH2, and 12 tumors (40%) revealed a strong beta-catenin overexpression. No BRAF and APC truncating mutations were identified, whereas K-ras mutations were detected in 9 ITACs (50%).

Conclusions: Our data confirm the phenotypic similarities at the genetic level between colorectal cancer and ITACs showing deregulation of K-Ras/BRAF and loss of heterozygosity (LOH) of chromosome 18q. By contrast, both frequency rate and type of inactivation of the APC-beta-catenin pathway differ in the 2 tumors, suggesting different gatekeeper events in the early development of ITAC (p16(INK4a) and TP53) and colorectal cancer (APC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma / genetics*
  • Adenomatous Polyposis Coli Protein / genetics
  • Carrier Proteins / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Colorectal Neoplasms / genetics
  • DNA Mismatch Repair
  • Gene Expression Regulation, Neoplastic
  • Genes, ras / genetics
  • Genotype
  • Humans
  • Loss of Heterozygosity
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics
  • Mutation
  • Nasal Cavity*
  • Nose Neoplasms / genetics*
  • Nuclear Proteins / genetics
  • Paranasal Sinus Neoplasms / genetics*
  • Phenotype
  • Proto-Oncogene Proteins B-raf / genetics
  • beta Catenin / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • Carrier Proteins
  • MLH1 protein, human
  • Nuclear Proteins
  • beta Catenin
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein