title: Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma.
abstract: OBJECTIVE
  For endometrial carcinoma, prognostic stratification methods do not satisfactorily identify patients with adverse outcome. Currently, histology, tumor grade and stage are used to tailoring surgical treatment and to determine the need for adjuvant treatment. Low-risk patients are not considered to require adjuvant therapy or staging lymphadenectomy. For patients with intermediate or high risk, some guidelines recommend tailoring adjuvant treatment according to additional negative prognostic factors. Our objective was to evaluate the biomarker potential of the ASRGL1 protein in endometrial carcinoma.
  
  
  METHODS
  Using The Human Protein Atlas (www.proteinatlas.org), the l-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1 expression was immunohistochemically evaluated with an extensively validated antibody on two independent endometrial carcinoma cohorts (n=229 and n=286) arranged as tissue microarrays. Staining results were correlated with clinical features.
  
  
  RESULTS
  Reduced expression of ASRGL1, defined as <75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In multivariate analysis the hazard ratios for disease-specific survival were 3.55 (95% CI=1.10-11.43; p=0.003) and 3.23 (95% CI=1.53-6.81; p=0.002) in the two cohorts, respectively. Of the 48 cases with Grade 3 Stage I tumor all disease-related deaths were associated with low ASRGL1 expression.
  
  
  CONCLUSIONS
  Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.
authors: Uppsala University, Department of Immunology, Genetics and Pathology, Sweden; Science for Life Laboratory, Uppsala, Sweden. Electronic address: Per-henrik.edqvist@igp.uu.se.
authors: Per-Henrik D
authors: PH
authors: Edqvist
authors: Department of Pathology, University of Turku, Turku, Finland; Department of Gynecology and Obstetrics, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital, Turku, Finland; Department of Gynecology and Obstetrics, Turku University Hospital, Turku, Finland.
authors: Jutta
authors: J
authors: Huvila
authors: Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden.
authors: Björn
authors: B
authors: Forsström
authors: Department of Pathology, Turku University Hospital, Turku, Finland.
authors: Lauri
authors: L
authors: Talve
authors: Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital, Turku, Finland.
authors: Olli
authors: O
authors: Carpén
authors: Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Helga B
authors: HB
authors: Salvesen
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Camilla
authors: C
authors: Krakstad
authors: Department of Gynecology and Obstetrics, University of Turku, Turku, Finland; Department of Gynecology and Obstetrics, Turku University Hospital, Turku, Finland.
authors: Seija
authors: S
authors: Grénman
authors: Atlas Antibodies AB, AlbaNova University Center, 106 91 Stockholm, Sweden.
authors: Henrik
authors: H
authors: Johannesson
authors: Atlas Antibodies AB, AlbaNova University Center, 106 91 Stockholm, Sweden.
authors: Oscar
authors: O
authors: Ljungqvist
authors: Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden.
authors: Mathias
authors: M
authors: Uhlén
authors: Uppsala University, Department of Immunology, Genetics and Pathology, Sweden; Science for Life Laboratory, Uppsala, Sweden.
authors: Fredrik
authors: F
authors: Pontén
authors: Department of Gynecology and Obstetrics, University of Turku, Turku, Finland; Department of Gynecology and Obstetrics, Turku University Hospital, Turku, Finland.
authors: Annika
authors: A
authors: Auranen
mesh_terms: D000368:Aged; D001215:Asparaginase / Q000096:biosynthesis* / Q000172:deficiency; D001324:Autoantigens / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018269:Carcinoma, Endometrioid / Q000201:enzymology* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; C466840:ASRGL1 protein, human; D001215:Asparaginase
keywords: Biomarker; Endometrial cancer; Immunohistochemistry; Pathology; Prognostic; Tissue microarray