Heidi Britton1, Leo Huang2, Amy Lum2, Samuel Leung2, Kathryn Shum2, Mruganka Kale1, Angela Burleigh1, Janine Senz2, Winnie Yang2, Melissa McConechy3, Stefan Kommoss4, Sara Brucker4, Aline Talhouk5, C Blake Gilks2, Jessica N McAlpine6. 1. Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 3. Contextual Genomics Inc., University of British Columbia, Vancouver, British Columbia, Canada. 4. Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Tübingen University Hospital, Tübingen, Germany. 5. Department of Gynecology and Obstetrics and Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada. 6. Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: jessica.mcalpine@vch.ca.
Abstract
OBJECTIVE: Approximately 15% of endometrial carcinomas (ECs) arise in young women who may wish to avoid surgical menopause and/or preserve fertility. Our aim was to evaluate the prognostic significance of Proactive Molecular risk classifier for Endometrial Carcinoma (ProMisE) in young (<50 yo) women with EC. METHODS: ProMisE was applied to a retrospective cohort of women with ECs <50 yo at diagnosis, and associations between the four ProMisE molecular subtypes (MMR deficient (MMRd), POLE mutated (POLE), p53 wild type (p53wt), and p53 abnormal (p53abn)) and clinicopathological parameters, including outcomes, were assessed. RESULTS: Of 257 ECs, there were 48 (19%) MMRd, 34 (13%) POLE, 164 (64%) p53wt and 11 (4%) p53abn. ProMisE subtypes were associated with differences in all measured clinicopathological parameters except for presence of synchronous ovarian tumours and fertility. Age at diagnosis was youngest and BMI highest in women with p53wt ECs. MMRd and p53abn tumours were more likely to be advanced stage (III/IV), high-risk (ESMO), and receive chemotherapy. ProMisE subtypes were strongly associated with outcomes (overall, disease-specific, and progression-free survival (p < 0.0001 for all)). Advanced stage, grade, LVSI, myometrial invasion and ESMO risk groups showed associations with some but not all survival parameters. ProMisE maintained a strong association with OS and DSS on multivariable analysis. CONCLUSIONS: ProMisE molecular classification is prognostic in young women with EC, enabling early stratification and risk assignment to direct care. Further studies can assess response to therapy, fertility, and cancer-related outcomes within the framework of molecular subtype.
OBJECTIVE: Approximately 15% of endometrial carcinomas (ECs) arise in young women who may wish to avoid surgical menopause and/or preserve fertility. Our aim was to evaluate the prognostic significance of Proactive Molecular risk classifier for Endometrial Carcinoma (ProMisE) in young (<50 yo) women with EC. METHODS: ProMisE was applied to a retrospective cohort of women with ECs <50 yo at diagnosis, and associations between the four ProMisE molecular subtypes (MMR deficient (MMRd), POLE mutated (POLE), p53 wild type (p53wt), and p53 abnormal (p53abn)) and clinicopathological parameters, including outcomes, were assessed. RESULTS: Of 257 ECs, there were 48 (19%) MMRd, 34 (13%) POLE, 164 (64%) p53wt and 11 (4%) p53abn. ProMisE subtypes were associated with differences in all measured clinicopathological parameters except for presence of synchronous ovarian tumours and fertility. Age at diagnosis was youngest and BMI highest in women with p53wt ECs. MMRd and p53abn tumours were more likely to be advanced stage (III/IV), high-risk (ESMO), and receive chemotherapy. ProMisE subtypes were strongly associated with outcomes (overall, disease-specific, and progression-free survival (p < 0.0001 for all)). Advanced stage, grade, LVSI, myometrial invasion and ESMO risk groups showed associations with some but not all survival parameters. ProMisE maintained a strong association with OS and DSS on multivariable analysis. CONCLUSIONS: ProMisE molecular classification is prognostic in young women with EC, enabling early stratification and risk assignment to direct care. Further studies can assess response to therapy, fertility, and cancer-related outcomes within the framework of molecular subtype.
Authors: Antonio Travaglino; Antonio Raffone; Diego Raimondo; Damiano Arciuolo; Giuseppe Angelico; Michele Valente; Giulia Scaglione; Nicoletta D'alessandris; Paolo Casadio; Frediano Inzani; Antonio Mollo; Angela Santoro; Renato Seracchioli; Gian Franco Zannoni Journal: Int J Gynaecol Obstet Date: 2021-10-11 Impact factor: 4.447
Authors: Diego Raimondo; Antonio Raffone; Antonio Travaglino; Manuela Maletta; Paolo Casadio; Marco Ambrosio; Anna Chiara Aru; Angela Santoro; Gian Franco Zannoni; Luigi Insabato; Antonio Mollo; Fulvio Zullo; Renato Seracchioli Journal: Int J Gynaecol Obstet Date: 2021-07-18 Impact factor: 4.447