title: YWHAE-rearranged high-grade endometrial stromal sarcoma: Two-center case series and response to chemotherapy.
abstract: YWHAE-rearranged high-grade endometrial stromal sarcoma (HG-ESS) is a rare, recently defined uterine sarcoma harboring t(10;17)(q22;p13) resulting in YWHAE-NUTM2A/B fusion. Chemotherapy sensitivity of metastatic YWHAE-rearranged HG-ESS is unknown. We reviewed the response to chemotherapy in women with YWHAE-rearranged HG-ESS to provide guidance for clinical management.
  
  
  
  We retrospectively identified patients diagnosed with YWHAE-rearranged HG-ESS who received treatment for metastatic disease at our institutions. Cytogenetics or fluorescence in situ hybridization were performed in all cases to confirm rearrangement and, in conjunction with histopathology, a diagnosis of YWHAE-rearranged HG-ESS. Patient demographics, tumor histology, surgical procedures, radiation therapy, chemotherapy and treatment responses were collected.
  
  
  
  Seven patients were identified with YWHAE-rearranged HG-ESS and met criteria for inclusion in this study. The median age at diagnosis was 45 (range 42-47). All patients had undergone hysterectomy with bilateral salpingo-oophorectomy. FIGO stage at diagnosis was IVB in four patients and a single patient each at stage IIIB, II or I. Median follow-up for the cohort was 27months (range 6-123). Six patients received anthracycline-based chemotherapy, with two of six achieving a complete radiologic response. One patient received gemcitabine and docetaxel, resulting in a partial response. For three patients who died from metastatic disease, survival from initial diagnosis was 33, 100 and 123months.
  
  
  
  For metastatic YWHAE-rearranged HG-ESS, prolonged disease control following diagnosis was seen, with notable responses to anthracycline-based therapy. This emphasizes the need for appropriate molecular testing of uterine mesenchymal malignancies and suggests that chemotherapy is an effective treatment option for metastatic YWHAE-rearranged HG-ESS.
authors.affiliation: Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hemming
authors.affiliation: Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wagner
authors.affiliation: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chiang
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.affiliation: Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: suzanne_george@dfci.harvard.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: George
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D036821:Endometrial Stromal Tumors / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D048948:14-3-3 Proteins; D043823:Taxoids; C482983:YWHAE protein, human; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine
keywords: Anthracyclines; Endometrial stromal sarcoma; Sarcoma; Uterine mesenchymal neoplasms