domingo, 1 de diciembre de 2019

Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer. - PubMed - NCBI

2019 Nov 19. pii: S0090-8258(19)31615-4. doi: 10.1016/j.ygyno.2019.10.028. [Epub ahead of print]

Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer.

Stasenko M1, Tunnage I1, Ashley CW2, Rubinstein MM3, Latham AJ4, Da Cruz Paula A2, Mueller JJ5, Leitao MM Jr5, Friedman CF4, Makker V4, Soslow RA6, DeLair DF7, Hyman DM4, Zamarin D4, Alektiar KM8, Aghajanian CA4, Abu-Rustum NR5, Weigelt B6, Cadoo KA9.

Author information

1: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
4: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA.
5: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA.
6: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA.
7: Department of Pathology, NYU Langone Medical Center, New York, NY, USA.
8: Weill Medical College of Cornell University, New York, NY, USA; Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
9: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Medical College of Cornell University, New York, NY, USA. Electronic address: cadook@mskcc.org.

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.