Computational and Immunohistochemical Analyses Highlight AXL as a Potential Prognostic Marker for Ovarian Cancer Patients

Anticancer Res. 2016 Aug;36(8):4155-63.

Abstract

Background/aim: The activation of the membrane tyrosine kinase AXL is implicated in the migration and invasion in several carcinomas, including ovarian cancer. Herein, we investigated the association of the expression of AXL transcript and protein to the aggressiveness of ovarian cancer, as well as to patient outcome.

Materials and methods: Overall and relapse-free survival were determined with respect to AXL transcript levels by computational analysis on two publicly available datasets containing data of gene expression from high-grade ovarian cancers (n=776). Immunohistochemical evaluation of AXL protein expression was then performed using a proprietary tissue microarray consisting of 62 ovarian cancers of different histology, grading and staging. Expression was analyzed for association with clinicopathological parameters, including survival.

Results: In both analyzed datasets, AXL transcript expression was significantly associated to both overall and relapse-free survival in high-grade ovarian cancers. Membrane expression of AXL protein was observed in 89% of the analyzed ovarian cancers. A significant correlation was found between AXL expression and serous histologic subtype, higher tumor grade and type II tumors. No significant association between AXL protein expression and patient survival was found in our cohort. AXL is frequently expressed in high-grade serous ovarian cancers and its expression is significantly associated to tumors displaying poor prognosis.

Conclusion: AXL is a potential prognostic marker for the most aggressive ovarian carcinomas.

Keywords: AXL; gene expression; immunohistochemistry; ovarian carcinoma; prognostic marker.

MeSH terms

  • Axl Receptor Tyrosine Kinase
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / diagnosis
  • Neoplasms, Glandular and Epithelial / enzymology*
  • Neoplasms, Glandular and Epithelial / mortality
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / mortality
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human