Immunohistochemistry to detect hereditary nonpolyposis colorectal cancer in young patients: the 7-year Auckland experience

Dis Colon Rectum. 2011 May;54(5):552-8. doi: 10.1007/DCR.0b013e31820e3265.

Abstract

Background: In accordance with the Bethesda Guidelines, Auckland's metropolitan hospitals routinely perform immunohistochemistry for mismatch repair proteins on the tumor specimens of all patients with colorectal cancer aged 50 years and younger. When loss of expression is evident, patients are offered genetic counseling and gene mutation analysis.

Objectives: This study aimed to determine the completeness of young patient capture over the first 7 years of routine testing, to find whether patients were referred for genetic testing, and to determine the proportion of patients found to have a mismatch repair gene mutation.

Design: This study retrospectively reviewed clinical, pathological, and genetic data.

Settings: The study was conducted at 3 public hospitals in Auckland, New Zealand.

Patients: All patients aged 50 years and younger treated for colorectal cancer at Auckland's metropolitan hospitals between January 2001 and December 2007 (n = 243) were included.

Main outcome measures: The loss of expression of mismatch repair proteins by immunohistochemistry, referral for genetic testing, and proportion with mismatch repair gene mutation were the main outcome measures.

Results: Two hundred fourteen (88%) eligible patients had immunohistochemical analysis of their tumor and 33 (14%) had loss of expression of one or more mismatch repair proteins. Twenty-six patients were referred for genetic counseling, of whom 22 underwent genetic testing. A mismatch repair gene mutation was identified in 10 patients.

Limitations: Seven patients with loss of expression of mismatch repair proteins by immunohistochemistry were not referred for genetic assessment.

Conclusions: We have identified a mismatch repair gene mutation diagnostic of hereditary nonpolyposis colorectal cancer in 5% of all patients with colorectal cancer who were aged 50 years and younger. Routine immunohistochemical prescreening has important clinical benefit for these patients and their relatives.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Base Pair Mismatch*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA, Neoplasm / analysis*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry / methods*
  • Incidence
  • Male
  • Middle Aged
  • New Zealand / epidemiology
  • Retrospective Studies
  • Time Factors
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm