Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer Journal Article

Authors: Stasenko, M.; Tunnage, I.; Ashley, C. W.; Rubinstein, M. M.; Latham, A. J.; Da Cruz Paula, A.; Mueller, J. J.; Leitao, M. M. Jr; Friedman, C. F.; Makker, V.; Soslow, R. A.; DeLair, D. F.; Hyman, D. M.; Zamarin, D.; Alektiar, K. M.; Aghajanian, C. A.; Abu-Rustum, N. R.; Weigelt, B.; Cadoo, K. A.
Article Title: Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer
Abstract: Objectives: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs). Methods: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410–468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins. Results: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment. Conclusions: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy. © 2019 Elsevier Inc.
Keywords: immunohistochemistry; adult; clinical article; protein expression; aged; cancer surgery; gene mutation; gene sequence; cancer recurrence; cancer adjuvant therapy; cancer patient; cancer radiotherapy; cancer staging; antineoplastic agent; endometrium carcinoma; cancer grading; cancer hormone therapy; mismatch repair; microsatellite instability; antineoplastic hormone agonists and antagonists; hereditary nonpolyposis colorectal cancer; dna directed dna polymerase epsilon; clinical outcome; cancer prognosis; human; female; priority journal; article; tumor-related gene; pole edm; pole exonuclease domain; recurrent endometrioid endometrial adenocarcinoma
Journal Title: Gynecologic Oncology
Volume: 156
Issue: 1
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2020-01-01
Start Page: 194
End Page: 202
Language: English
DOI: 10.1016/j.ygyno.2019.10.028
PUBMED: 31757464
PROVIDER: scopus
PMCID: PMC6980651
Notes: Article -- Export Date: 3 February 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Vicky Makker
    149 Makker
  2. Kaled M Alektiar
    287 Alektiar
  3. Mario Leitao
    442 Leitao
  4. Dmitriy Zamarin
    137 Zamarin
  5. Robert Soslow
    754 Soslow
  6. David Hyman
    349 Hyman
  7. Karen Anne Cadoo
    102 Cadoo
  8. Britta Weigelt
    443 Weigelt
  9. Jennifer Jean Mueller
    99 Mueller
  10. Alicia Latham
    30 Latham
  11. Charles Warner Ashley
    11 Ashley