title: Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma.
abstract: BACKGROUND
  Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes. Estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR) have been implicated in the pathophysiology of other cancer types. We sought to comprehensively determine temporal expression patterns of these receptors in LS.
  
  
  METHODS
  We analyzed 561 histologically subtyped LS specimens from 354 patients for expression of ER, PR, and AR by immunohistochemistry (IHC) using diagnostic-grade reagents and protocols. The fractions of positively stained tumor cells were scored within each specimen. IHC scores were compared across LS subtypes using the Kruskal-Wallis test, and subtypes were compared using Dunn's post-hoc test. Ages of patients with receptor-positive vs. -negative LS were compared by t-test. Genders and races were compared for hormone receptor positivity using Fisher's exact test and Chi-square analysis, respectively. Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p< 0.05 was considered significant.
  
  
  RESULTS
  ER and AR were frequently expressed in LS, while few tumors expressed PR. Most of the ER + and AR + samples were of the well-differentiated LS subtype. A smaller fraction of de-differentiated LS expressed ER or AR, but expression was common within well-differentiated regions of tumors histologically classified as de-differentiated LS. In LS specimens from patients who underwent multiple surgeries over time, receptor expression frequently changed over time, which may be attributable in part to intratumor heterogeneity, varying degrees of de-differentiation, and biopsy bias. ER and AR were frequently co-expressed. Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis. Receptor expression was not associated with altered recurrence-free survival.
  
  
  CONCLUSIONS
  ER and AR are commonly expressed in LS, particularly in well-differentiated tumors. These data warrant further functional study to determine receptor function in LS, and the potential efficacy of anti-hormone therapies for the treatment of patients with LS.
authors.affiliation: Departments of Surgical Oncology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX, USA.
authors.forename: Davis R
authors.initials: DR
authors.lastname: Ingram
authors.affiliation: Departments of Pharmacology & Toxicology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, HB-7936, Lebanon, NH 03756, USA.
authors.forename: Lloye M
authors.initials: LM
authors.lastname: Dillon
authors.affiliation: Departments of Surgical Oncology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX, USA.
authors.forename: Dina Chelouche
authors.initials: DC
authors.lastname: Lev
authors.affiliation: Departments of Surgical Pathology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lazar
authors.affiliation: Department of Pathology, Mount Sinai Medical Center, One Gustave L. Levy Pl, New York, NY, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Demicco
authors.affiliation: Departments of Surgery, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH, USA.
authors.forename: Burton L
authors.initials: BL
authors.lastname: Eisenberg
authors.affiliation: Departments of Pharmacology & Toxicology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, HB-7936, Lebanon, NH 03756, USA.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Miller