. 2022 Dec;35(12):1974-1982.

doi: 10.1038/s41379-022-01165-w. Epub 2022 Oct 14.

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

Emily F Thompson¹, Jutta Huvila^{1

2}, Amy Jamieson³, Samuel Leung⁴, Amy Lum¹, Saul Offman⁵, Alice Lytwyn⁶, Mona Lisa Sur⁶, Lynn Hoang⁷, Julie Irving⁸, Nicholas van der Westhuizen⁸, Chantale Morin⁹, Cyrille Bicamumpaka¹⁰, Nazilla Azordegan¹⁰, François Gougeon¹¹, Kaoutar Ennour-Idrissi¹², Janine Senz¹, Melissa K McConechy¹³, Rosalia Aguirre-Hernandez¹³, Victoria Lui¹⁴, Carolyn Kuo¹⁵, Cassidy Bell¹⁶, Taylor Salisbury⁷, James Lawson¹⁷, Ellen He¹⁷, Shanzhao Wang¹, Derek Chiu¹, Sarah Kean¹⁸, Vanessa Samouëlian¹⁹, Shannon Salvador²⁰, Walter Gotlieb²⁰, Limor Helpman²¹, Stephanie Scott²², Christoph Wohlmuth^{23

24}, Danielle Vicus²⁴, Marie Plante²⁵, Aline Talhouk¹, David Huntsman¹, Carlos Parra-Herran²⁶, Mary Kinloch²⁷, Katherine Grondin⁹, C Blake Gilks²⁸, Jessica N McAlpine³; Society of Gynecologic Oncologists of Canada (CoP, Translational Research)

Collaborators, Affiliations

Collaborators

Society of Gynecologic Oncologists of Canada (CoP, Translational Research):
Jessica McAlpine, Anita Agrawal, Omar Al-Nourhji, Alon Altman, Marcus Bernardini, C Bicamumpaka, Mark Carey, Blaise Clarke, Nazila Azordegan, Bojana Djordjevic, Laurie Elit, Alex Ferenczy, Sarah Finlayson, Anthony Fyles, Hugo Garneau, France Gauthier, Prafull Ghatage, Blake Gilks, Walter Gotlieb, Katherine Grondin, Kathy Han, Limor Helpman, Hal Hirte, Fleur Huang, Julie Irving, Sarah Kean, Katharina Kieser, Mary Kinlloch, Iwa Kong, Aalok Kumar, Janice 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, Vanessa Samouelian, Stephanie Scott, Anna Tinker, Alicia Tone, Danielle Vicus, Stephen Welch, Nicholas Westhuizen, Katarzyna Jerzak, Amy Jamieson

Affiliations

¹ Department of Molecular Oncology, University of British Columbia, Vancouver, BC, Canada.
² Department of Pathology, University of Turku, Turku University Hospital, Turku, Finland.
³ Department of Gynaecology and Obstetrics and Division of Gynaecologic Oncology, University of British Columbia, Vancouver, BC, Canada.
⁴ Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC, Canada.
⁵ Department of Pathology and Laboratory Medicine, Dalhousie University, Halifax, NS, Canada.
⁶ Department of Pathology and Molecular Medicine, McMaster University and The Juravinski Hospital and Cancer Centre, Hamilton, ON, Canada.
⁷ Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada.
⁸ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
⁹ Pathology Department, Centre Hospitalier Universitaire de Québec at Laval University and L'Hôtel-Dieu de Québec, Quebec, QC, Canada.
¹⁰ Department of Pathology, University of Manitoba, Winnipeg, MB, Canada.
¹¹ Department of Molecular Biology, Medical Biochemistry and Pathology, Centre Hospitalier Universitaire de Montréal at Université de Montréal, Montreal, QC, Canada.
¹² Department of Molecular Biology, Medical Biochemistry and Pathology, Centre Hospitalier Universitaire de Québec at Université de Laval, Quebec, QC, Canada.
¹³ Canexia Health, Vancouver, BC, Canada.
¹⁴ Faculty of Science, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Obstetrics, Gynecology and Reproductive Sciences Residency Program, University of Manitoba, Winnipeg, MB, Canada.
¹⁶ MD Undergraduate Program, University of Saskatchewan, Saskatoon, SK, Canada.
¹⁷ MD undergraduate program, University of British Columbia, Vancouver, BC, Canada.
¹⁸ Division of Gynecologic Oncology, University of Manitoba, Winnipeg, MB, Canada.
¹⁹ Department of Obstetrics and Gynecology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
²⁰ Division of Gynecologic Oncology, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, QC, Canada.
²¹ Division of Gynecologic Oncology, McMaster University and The Juravinski Hospital and Cancer Centre, Hamilton, ON, Canada.
²² Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Dalhousie University, Halifax, NS, Canada.
²³ Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.
²⁴ Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of Toronto, Toronto, ON, Canada.
²⁵ Department of Obstetrics, Gynecology and Reproduction, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Laval University, Quebec, QC, Canada.
²⁶ Department of Laboratory Medicine and Pathobiology University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁷ Department of Pathology and Laboratory Medicine, University of Saskatchewan and Saskatoon City Hospital, Saskatoon, SK, Canada.
²⁸ Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada. blake.gilks@vch.ca.

PMID: 36241860
DOI: 10.1038/s41379-022-01165-w

Free article

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

Emily F Thompson et al. Mod Pathol. 2022 Dec.

Free article

. 2022 Dec;35(12):1974-1982.

doi: 10.1038/s41379-022-01165-w. Epub 2022 Oct 14.

Authors

Collaborators

Society of Gynecologic Oncologists of Canada (CoP, Translational Research):
Jessica McAlpine, Anita Agrawal, Omar Al-Nourhji, Alon Altman, Marcus Bernardini, C Bicamumpaka, Mark Carey, Blaise Clarke, Nazila Azordegan, Bojana Djordjevic, Laurie Elit, Alex Ferenczy, Sarah Finlayson, Anthony Fyles, Hugo Garneau, France Gauthier, Prafull Ghatage, Blake Gilks, Walter Gotlieb, Katherine Grondin, Kathy Han, Limor Helpman, Hal Hirte, Fleur Huang, Julie Irving, Sarah Kean, Katharina Kieser, Mary Kinlloch, Iwa Kong, Aalok Kumar, Janice 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, Vanessa Samouelian, Stephanie Scott, Anna Tinker, Alicia Tone, Danielle Vicus, Stephen Welch, Nicholas Westhuizen, Katarzyna Jerzak, Amy Jamieson

Affiliations

¹ Department of Molecular Oncology, University of British Columbia, Vancouver, BC, Canada.
² Department of Pathology, University of Turku, Turku University Hospital, Turku, Finland.
³ Department of Gynaecology and Obstetrics and Division of Gynaecologic Oncology, University of British Columbia, Vancouver, BC, Canada.
⁴ Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC, Canada.
⁵ Department of Pathology and Laboratory Medicine, Dalhousie University, Halifax, NS, Canada.
⁶ Department of Pathology and Molecular Medicine, McMaster University and The Juravinski Hospital and Cancer Centre, Hamilton, ON, Canada.
⁷ Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada.
⁸ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
⁹ Pathology Department, Centre Hospitalier Universitaire de Québec at Laval University and L'Hôtel-Dieu de Québec, Quebec, QC, Canada.
¹⁰ Department of Pathology, University of Manitoba, Winnipeg, MB, Canada.
¹¹ Department of Molecular Biology, Medical Biochemistry and Pathology, Centre Hospitalier Universitaire de Montréal at Université de Montréal, Montreal, QC, Canada.
¹² Department of Molecular Biology, Medical Biochemistry and Pathology, Centre Hospitalier Universitaire de Québec at Université de Laval, Quebec, QC, Canada.
¹³ Canexia Health, Vancouver, BC, Canada.
¹⁴ Faculty of Science, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Obstetrics, Gynecology and Reproductive Sciences Residency Program, University of Manitoba, Winnipeg, MB, Canada.
¹⁶ MD Undergraduate Program, University of Saskatchewan, Saskatoon, SK, Canada.
¹⁷ MD undergraduate program, University of British Columbia, Vancouver, BC, Canada.
¹⁸ Division of Gynecologic Oncology, University of Manitoba, Winnipeg, MB, Canada.
¹⁹ Department of Obstetrics and Gynecology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
²⁰ Division of Gynecologic Oncology, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, QC, Canada.
²¹ Division of Gynecologic Oncology, McMaster University and The Juravinski Hospital and Cancer Centre, Hamilton, ON, Canada.
²² Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Dalhousie University, Halifax, NS, Canada.
²³ Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.
²⁴ Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of Toronto, Toronto, ON, Canada.
²⁵ Department of Obstetrics, Gynecology and Reproduction, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Laval University, Quebec, QC, Canada.
²⁶ Department of Laboratory Medicine and Pathobiology University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁷ Department of Pathology and Laboratory Medicine, University of Saskatchewan and Saskatoon City Hospital, Saskatoon, SK, Canada.
²⁸ Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, BC, Canada. blake.gilks@vch.ca.

PMID: 36241860
DOI: 10.1038/s41379-022-01165-w

Abstract

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.

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References

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous