The Value of Prospective Analysis of Mismatch Repair by Immunohistochemistry in Colorectal Cancer in the Irish Setting
R Geraghty, AA Maguire, D Kevans, D Keegan, J O'Sullivan, H Mulcahy, D O'Donoghue, J Hyland, D Winter, PR O'Connell, K Sheahan. St Vincent's University Hospital and Centre for Colorectal Disease, Dublin, Ireland
Background: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) accounts for 1-3% of all colorectal cancer (CRC) cases. Immunohistochemistry (IHC) for mismatch repair (MMR) proteins can aid in detecting these patients. Most CRC cases with deficient MMR (dMMR) status detected by IHC are sporadic and have a better prognosis than proficient MMR (pMMR) cases. Stratification of patients according to MMR status also assists in a more tailored approach to the use of adjuvant treatment. Since 2004, we have performed MMR IHC on all new CRC cases.
Design: Cases with IHC for MMR proteins MLH1, PMS2, MSH2 and MSH6 were identified from our database of 3130 patients. Clinical & pathological details were documented.
Results: IHC was performed on 752 cases. Median age at diagnosis was sixty-nine years. Loss of MMR protein expression was observed in 9%(n=67) of cases. There was loss of MLH1 & PMS2 in 81% (n=54), loss of MSH2 & MSH6 in 18% n=12) and exclusive loss of MSH6 in 1% (n=1).
Mismatch repair protein status and clinicopathological variablesdMMR deficient MMR protein, pMMR proficient MMR protein
|Family history CRC||32%||19%||0.013|
|Right sided CRC||72%||29%||<0.001|
|Large tumour size (7-16 cm)||37%||14%||<0.001|
|Stage IV CRC||3%||18%||<0.001|
|Infiltrative tumour margin||39%||60%||0.001|
Specific HNPCC-associated mutations were identified in 8/67 cases (12%) of dMMR cases, 3/8 (37.5%) of whom were not suspected by Amsterdam criteria.
Conclusions: dMMR status was identified in 9% of CRC cases which is comparable to rates seen in other populations. dMMR cases were more likely to have a family history of CRC, synchronous & metachronous tumours & associated with larger tumour size, mucinous and poor differentiation. Adverse histological features such as lymphovascular invasion & infiltrative margin were less frequent in dMMR cases, with stage IV tumours in only 3% of cases. IHC for MMR identified eight HNPCC cases, focused the search for the specific mutation and led to appropriate screening and surveillance of patients and affected family members.
Monday, March 9, 2009 1:00 PM
Poster Session II # 63, Monday Afternoon