Comparison of Alu-PCR, microsatelite instability, and immunohistochemical analyses in finding features characteristic for hereditary nonpolyposis colorectal cancer

J Cancer Res Clin Oncol. 2001 Sep;127(9):565-9. doi: 10.1007/s004320100261.

Abstract

Purpose: To evaluate and compare alterations detected by Alu-PCR, microsatellite instability (MI), and absence of hMLH1 and hMSH2 protein expression measured by immunohistochemical (IHC) analyses as features characteristic of hereditary nonpolyposis colorectal cancer (HNPCC).

Methods: Alu-PCR, MI, and IHC analyses were performed in two groups of patients: (A) HNPCC diagnosed definitively or with high probability (11 patients); (B) sporadic late-onset colorectal cancers (15 patients).

Results: Quantitative alterations recorded by Alu-PCR were not characteristic for Lynch syndrome, occurring more frequently in sporadic late-onset CRC (73% in group B vs 45% in group A). Qualitative changes (occurrence of additional peaks or shifts) have been found to be associated with HNPCC with odds ratio (OR) 2.4, specificity approximately 70% and sensitivity approximately 55%. Findings in MI and IHC analyses have been recognized as features more characteristic of HNPCC suggesting Lynch syndrome with OR 4.8, specificity approximately 80%, sensitivity approximately 55% (MI) and OR 8.0, specificity approximately 93%, sensitivity approximately 36% (IHC).

Conclusion: Molecular techniques allowing identification of patients with a high probability of having HNPCC include IHC and MI analyses. Our results suggest that their replacement by Alu-PCR analysis in diagnosis of HNPCC is not justified.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alu Elements / genetics*
  • Carrier Proteins
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism*
  • DNA-Binding Proteins*
  • Diagnosis, Differential
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • Microsatellite Repeats / genetics*
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein