Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer
| Autor: | Charles W. Ashley, Kaled M. Alektiar, Britta Weigelt, Mario M. Leitao, Deborah F. DeLair, Karen Cadoo, D. Zamarin, Irina Tunnage, Arnaud Da Cruz Paula, Vicky Makker, Nadeem R. Abu-Rustum, Alicia Latham, Jennifer J. Mueller, Maria M. Rubinstein, David M. Hyman, Carol Aghajanian, Robert A. Soslow, Marina Stasenko, Claire F. Friedman |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine Oncology medicine.medical_specialty DNA Mismatch Repair Article Cohort Studies 03 medical and health sciences 0302 clinical medicine Internal medicine Adjuvant therapy Humans Medicine Prospective Studies Neoplasm Metastasis Stage (cooking) Poly-ADP-Ribose Binding Proteins Aged Neoplasm Staging business.industry Endometrial cancer Obstetrics and Gynecology Microsatellite instability DNA Polymerase II Middle Aged Prognosis medicine.disease Lynch syndrome Endometrial Neoplasms 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cohort Female Microsatellite Instability DNA mismatch repair Neoplasm Grading Neoplasm Recurrence Local business Carcinoma Endometrioid Progressive disease |
| Zdroj: | Gynecol Oncol |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2019.10.028 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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