Use of mismatch repair immunohistochemistry and microsatellite instability testing: exploring Canadian practices.
BACKGROUND
The mismatch repair (MMR) status of tumors is being increasingly recognized as a prognostic, predictive, and possible germline predisposition/Lynch syndrome (LS) biomarker in colorectal cancer and other cancer types, particularly in endometrial cancer. Current methods (clinical history and tumor morphology) to predict MMR deficiency (dMMR) are suboptimal, and implementation of reflex laboratory testing of appropriate tumors has been recommended, a strategy requiring test standardization and clinical coordination.


METHODS
Two web-based questionnaires were administered, a general and a specialist laboratory questionnaire, to establish the availability of such tests, requisite clinical/pathology integration, current mode of test initiation, reporting and recommendation practices, and education and attitudes among pathologists. Technical aspects were reviewed on the basis of specialist laboratory practice.


RESULTS
Of 76 respondents, 21.5% were unaware or were uncertain whether they had access to MMR immunohistochemistry. Although 78.9% of respondents had access to such testing, an integrated approach to the identification of patients with LS is lacking, being limited to just 9 centers. The majority (70%) of testing is clinician initiated, with variable implementation of reflex testing and divergent practices in recommendation to test. Standardized reporting is lacking in many centers. Education on MMR in endometrial cancer is poor compared with that in colorectal cancer (P<0.0001).


CONCLUSIONS
This multicenter questionnaire highlights heterogenous practices in dMMR testing and LS identification, both in clinical terms and with regard to technical aspects of testing. An integrated multidisciplinary approach is lacking, and there is a need to educate physicians and resolve ethical issues. A Canadian consensus statement and national guidelines on dMMR testing are urgently needed, requiring input from pathologists, clinicians, and genetic counselors.
Department of Pathology, University of British Columbia, Vancouver, BC, Canada.
Steve E
SE
Kalloger
Ghassan
G
Allo
Anna Marie
AM
Mulligan
Aaron
A
Pollett
Melyssa
M
Aronson
Steven
S
Gallinger
Emina E
EE
Torlakovic
Blaise Alexander
BA
Clarke
D002170:Canada; D053843:DNA Mismatch Repair; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000706:statistics & numerical data*; D020407:Internet; D053842:Microsatellite Instability; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics; D011364:Professional Practice / Q000706:statistics & numerical data; D011379:Prognosis; D011795:Surveys and Questionnaires