Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer

Weiya Xia, Yongkun Wei, Yi Du, Jinsong Liu, Bin Chang, Ng Luen Yu, Long Fei Huo, Stephanie Miller, Mien Chie Hung

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

The epidermal growth factor receptor (EGFR) has previously been detected in the nucleus of cancer cells and primary tumors. We have reported that EGFR translocates from the plasma membrane to the nucleus. Accumulation of nuclear EGFR is linked to increased DNA synthesis and proliferation; however, the pathological significance of nuclear EGFR is not completely understood. Here, we sought to determine the predictive value of EGFR for the survival of ovarian cancer patients, through the examination of 221 cases of ovarian cancer tissues by immunohistochemical analysis to determine nuclear EGFR expression. In addition, we also examined cyclin D1 and Ki-67 through immunohistochemisty. Furthermore, we examined nuclear EGFR levels in ovarian cancer cell lines treated with EGF, and primary ovarian tumor tissue using immunofluorescence analysis. Nuclear fractions extracted from serum-starved cells treated with or without EGF were subjected to SDS-PAGE and Western blot analyses. We found that 28.3% of the cohort had high levels of nuclear EGFR, while 22.5% had low levels of nuclear EGFR, and 49.2% were negative for nuclear EGFR. Importantly, there was an inverse correlation between high nuclear EGFR, cyclin D1, and Ki-67 with overall survival (P<0.01, P<0.09, P<0.041). Additionally, nuclear EGFR correlated positively with increased levels of cyclin D1 and Ki-67, both indicators for cell proliferation. Our findings indicate a pathological significance of nuclear EGFR that might be important for predicting clinical prognosis of ovarian cancer patients.

Original languageEnglish (US)
Pages (from-to)610-617
Number of pages8
JournalMolecular Carcinogenesis
Volume48
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

Keywords

  • Cyclin D1
  • EGFR
  • Nucleus
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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