Loss of ASRGL1 Expression Is an Independent Biomarker for Disease-Specific Survival in Endometrioid Endometrial Carcinoma

Gynecol Oncol. 2015 Jun;137(3):529-37. doi: 10.1016/j.ygyno.2015.03.055. Epub 2015 Apr 7.

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.

Keywords: Biomarker; Endometrial cancer; Immunohistochemistry; Pathology; Prognostic; Tissue microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asparaginase / biosynthesis*
  • Asparaginase / deficiency
  • Autoantigens / biosynthesis*
  • Biomarkers, Tumor / biosynthesis*
  • Carcinoma, Endometrioid / enzymology*
  • Carcinoma, Endometrioid / pathology
  • Cohort Studies
  • Disease-Free Survival
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Retrospective Studies

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • ASRGL1 protein, human
  • Asparaginase