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Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification

2022; Elsevier BV; Volume: 35; Issue: 12 Linguagem: Inglês

10.1038/s41379-022-01165-w

1530-0285

Emily F. Thompson, Jutta Huvila, Amy Jamieson, Samuel Leung, Amy Lum, Saul Offman, Alice Lytwyn, Mona Lisa Sur, Lynn Hoang, Julie Irving, Nicholas van der Westhuizen, Chantale Morin, Cyrille Bicamumpaka, Nazilla Azordegan, F. Gougeon, Kaoutar Ennour-Idrissi, Janine Senz, Melissa K. McConechy, Rosalía Aguirre-Hernández, Victoria Lui, Carolyn Kuo, Cassidy Bell, Taylor Salisbury, James Lawson, Ellen He, Shanzhao Wang, Derek S. Chiu, Sarah Kean, Vanessa Samouëlian, Shannon Salvador, Walter H. Gotlieb, Limor Helpman, Stephanie Scott, Christoph Wohlmuth, Danielle Vicus, Marie Plante, Aline Talhouk, David G. Huntsman, Carlos Parra‐Herran, Mary Kinloch, Katherine Grondin, C. Blake Gilks, Jessica N. McAlpine, Jessica N. McAlpine, Anita Agrawal, Omar Al‐Nourhji, Alon D. Altman, Marcus Q. Bernardini, Cyrille Bicamumpaka, Mark Carey, Blaise Clarke, Nazila Azordegan, Bojana Djordjevic, Laurie Elit, Alex Ferenczy, Sarah Finlayson, Anthony Fyles, Hugo Garneau, France Gauthier, Prafull Ghatage, C. Blake Gilks, Walter H. Gotlieb, Katherine Grondin, Kathy Han, Limor Helpman, Hal W. Hirte, Fleur Huang, Julie Irving, Sarah Kean, Katharina Kieser, Mary Kinlloch, Iwa Kong, Aalok Kumar, Janice S. Kwon, Sandra Lee, Eric Leung, Helen Mackay, Eve‐Lyne Marchand, Justin Mcginnis, Dianne Miller, Chantale Morin, Gregg Nelson, Saul Offman, Manuela Pelmus, Annick Pina, Marie Plante, Anna Plotkin, Diane Provencher, Shannon Salvador, Stephanie Scott, Anna V. Tinker, Alicia Tone, Danielle Vicus, Stephen Welch, Nicholas Westhuizen, Katarzyna J. Jerzak, Amy Jamieson,

Ovarian cancer diagnosis and treatment

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5–95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1–41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.