ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival

Br J Cancer. 2011 May 10;104(10):1602-10. doi: 10.1038/bjc.2011.117. Epub 2011 Apr 19.

Abstract

Background: The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephaly-associated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers.

Methods: Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data.

Results: A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival.

Conclusion: Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Ovarian Epithelial
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cytoskeletal Proteins
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Spindle Apparatus / metabolism
  • Survival Analysis

Substances

  • ASPM protein, human
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • MCPH1 protein, human
  • Nerve Tissue Proteins