A survey of the current provision of screening tumours for mismatch repair deficiency in Australia: An Inherited Cancer Connect Partnership (ICCon) initiative

Alex Boussioutasa,b,c, Sue Shanleya, Robyn Warde, Nicholas Pachterd,i, Finlay Macraeb,c, Stephen Fox a, Gillian Mitchella,f, , Elaine Duxburyg, Daniel Buchananc, Amanda Spurdleh, Lyon Mascarenhasa, Rebecca Driessena

aPeter MacCallum Cancer Centre, Melbourne, VIC, Australia

b Royal Melbourne Hospital, Melbourne, VIC, Australia

cUniversity of Melbourne, Melbourne, VIC, Australia

dKing Edward Hospital, Perth, WA, Australia

ePrince of Wales Hospital, NSW, Australia

fBC Cancer Agency, Vancouver, BC, Canada

gCancer Action Victoria, Victoria, Australia

hQIMR Berghofer Medical Research Institute

I Department of Medicine & Pharmacology, University of Western Australia

Background:Previous studies have demonstrated that screening for LS in all new cases of colorectal cancer (CRC)& endometrial cancer (EC) is feasible and detects a significant number of patients with germline MMR mutations1,2,3

Aim:To survey current availability of screening for tumour MMR deficiency and the triggers for MMR assessment at point of colorectal/endometrial cancer diagnosis in both public and private laboratories throughout Australia.

Methods:Heads of all RCPA accredited laboratories in Australia were invited by email to participate in an online survey. The proportions of laboratories offering testing for mismatch repair immunohistochemistry (MMR IHC), IHC + microsatellite instability (MSI), BRAF V600E mutation t and MLH1 promoter methylation were calculated.

Results:From39 participatinglaboratories;75 % had MMR IHC capability, 20 % were able tooffer both IHC+MSI testing, and remaining 5% did neither. For CRCs, majority laboratoriesare routinely screening all specimens for MMR(46%),7% undertake testing on clinician request while 32 %select cases based on “red flag” criteria. ForEC, 11 % labs are universally screening all cases of EC processed in the lab, 42 % only test for MMR upon clinician request while 29% test on “red flag” cases. Some reported testing on “red flag” cases in addition to clinician request, 15% for CRC and 8% for EC. Labs also reported having the capacity to offer MLH1 methylation testing (14%) and BRAF V600E mutation testing (51%).

Conclusion: It is promising that a large proportion of laboratories have already established universal screening of all new cases of CRC for evidence of MMR deficiency. A much smaller number of labs are undertaking universal MMR screening in new cases of EC and instead the majority that do test only do so when triggered by clinician’s request. The strong published evidence for universal testing of new cases of CRC and EC for MMR deficiency warrants a standardised national policy for screening MMR mutations.