RT Journal Article
SR Electronic
T1 Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP ijgc-2020-001927
DO 10.1136/ijgc-2020-001927
A1 Soyoun Rachel Kim
A1 Alicia Tone
A1 Raymond Kim
A1 Matthew Cesari
A1 Blaise Clarke
A1 Lua Eiriksson
A1 Tae Hart
A1 Melyssa Aronson
A1 Spring Holter
A1 Alice Lytwyn
A1 Manjula Maganti
A1 Leslie Oldfield
A1 Steven Gallinger
A1 Marcus Q Bernardini
A1 Amit M Oza
A1 Bojana Djordjevic
A1 Jordan Lerner-Ellis
A1 Emily Van de Laar
A1 Danielle Vicus
A1 Trevor J Pugh
A1 Aaron Pollett
A1 Sarah Elizabeth Ferguson
YR 2020
UL http://ijgc.bmj.com/content/early/2020/10/15/ijgc-2020-001927.abstract
AB Objectives For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests.Methods 30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing.Results Of 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a PMS2 pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium.Conclusions There was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.