Endoscopy 2005; 37 - A19
DOI: 10.1055/s-2005-922881

Immunohistochemistry as an aid to the diagnosis of HNPCC

R Geraghty 1, D Keegan 1, E Fox 1, D Leahy 1, A Green 1, JM Hyland 1, K Sheahan 1, DP O'Donoghue 1
  • 1Centre for Colorectal Disease, St. Vincent's University Hospital, Conway Institute, University College Dublin, National Centre for Medical Genetics, Dublin

Aims: Assess the value of routine Immunohistochemistry (IHC) for loss of Mismatch Repair Proteins (MMR) in the detection of Hereditary Non Polyposis Colorectal Cancer (HNPCC).

Introduction: Family history (FH) is a risk factor for the development of Colorectal cancer (CRC) and this is particularly so for HNPCC. Identification of HNPCC relies on a detailed FH which is not always known and does not allow for small families or index cases. Many cases may thus be overlooked. Loss of MMRs, which can be detected by IHC, can serve as surrogate markers in this setting.

Results: Resection specimens from 100 consecutive patients with CRC were tested for the loss of the MMR proteins. Eleven (11%) showed MMR loss: 7– MLH1; 3– MSH2 and 6; 1– MSH6 alone. The profile of the 7 patients with loss on MLH1 suggests sporadic CRC due to gene silencing. The 3 patients with MSH2 and 6 losses are all microsatellite unstable, have no FH and likely represent index cases of HNPCC. A further patient in this series satisfies the Amsterdam Criteria without loss of MMR.

Conclusions: IHC is a relatively simple method that may aid the diagnosis of HNPCC and detect index cases.