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 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2020 -- Source: Scopus |
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