[581] 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 variables

	dMMR	pMMR	p value
Female	61%	43%	0.004
Family history CRC	32%	19%	0.013
Synchronous CRC	16%	7%	0.005
Metachronous CRC	13%	3%	<0.001
Right sided CRC	72%	29%	<0.001
Large tumour size (7-16 cm)	37%	14%	<0.001
Mucinous (>10%)	22%	9%	0.003
Poor differentiation	40%	13%	<0.001
Stage IV CRC	3%	18%	<0.001
Infiltrative tumour margin	39%	60%	0.001
Lymphovascular invasion	30%	49%	0.006

dMMR deficient MMR protein, pMMR proficient MMR protein

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.
Category: Gastrointestinal

Monday, March 9, 2009 1:00 PM

Poster Session II # 63, Monday Afternoon