TY - JOUR
T1 - Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer
AU - Stasenko, Marina
AU - Tunnage, Irina
AU - Ashley, Charles W.
AU - Rubinstein, Maria M.
AU - Latham, Alicia J.
AU - Da Cruz Paula, Arnaud
AU - Mueller, Jennifer J.
AU - Leitao, Mario M.
AU - Friedman, Claire F.
AU - Makker, Vicky
AU - Soslow, Robert A.
AU - DeLair, Deborah F.
AU - Hyman, David M.
AU - Zamarin, Dimitriy
AU - Alektiar, Kaled M.
AU - Aghajanian, Carol A.
AU - Abu-Rustum, Nadeem R.
AU - Weigelt, Britta
AU - Cadoo, Karen A.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - POLE EDM
KW - POLE exonuclease domain
KW - Recurrent endometrioid endometrial adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=85075816761&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2019.10.028
DO - 10.1016/j.ygyno.2019.10.028
M3 - Article
C2 - 31757464
AN - SCOPUS:85075816761
SN - 0090-8258
VL - 156
SP - 194
EP - 202
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -