Open AccessScreening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers
Author(s) -
O'Kane Grainne M.,
Ryan Éanna,
McVeigh Terri P.,
Creavin Ben,
Hyland John MP.,
O'Donoghue Diarmuid P.,
Keegan Denise,
Geraghty Robert,
Flannery Delia,
Nolan Carmel,
Donovan Emily,
Mehigan Brian J.,
McCormick Paul,
Muldoon Cian,
Farrell Michael,
Shields Conor,
Mulligan Niall,
Kennedy Michael John,
Green Andrew J.,
Winter Desmond C.,
MacMathuna Padraic,
Sheahan Kieran,
Gallagher David J.
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1025
Subject(s) - medicine , lynch syndrome , colorectal cancer , dna mismatch repair , oncology , population , cancer , microsatellite instability , referral , family medicine , allele , environmental health , microsatellite , gene , biochemistry , chemistry
Reflex immunohistochemistry ( rIHC ) for mismatch repair ( MMR ) protein expression can be used as a screening tool to detect Lynch Syndrome ( LS ). Increasingly the mismatch repair‐deficient ( dMMR ) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres ( CC s). CRC databases were analyzed from January 2005–December 2013. CC 1 performs IHC upon physician request, CC 2 implemented rIHC in November 2008, and CC 3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services ( CGS ), and the number of LS patients per center was determined. 3906 patients were included over a 9‐year period. dMMR CRC s were found in 32/153 (21%) of patients at CC 1 and 55/536 (10%) at CC 2, accounting for 3% and 5% of the CRC population, respectively. At CC 3, 182/1737 patients (10%) had dMMR CRC s ( P < 0.001). Additional testing for the BRAF V600E mutation, was performed in 49 patients at CC 3 prior to CGS referral, of which 29 were positive and considered sporadic CRC . Referrals to CGS were made in 66%, 33%, and 30% of eligible patients at CC 1, CC 2, and CC 3, respectively. LS accounted for CRC in eight patients (0.8%) at CC 1, eight patients (0.7%) at CC 2, and 20 patients (1.2%) at CC 3. Cascade testing of patients with dMMR CRC was not completed in 56%. Universal screening increases the detection of dMMR tumors and LS kindreds. Successful implementation of this approach requires adequate resources for appropriate downstream management of these patients.