1. ¹Department of Gynaecologic Oncology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands
2. ²Department of Pathology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands
3. ³Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
4. ⁴Endocrine Cancer Group, Western General Hospital, Edinburgh Cancer Research Centre, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK
5. ⁵Department of Epidemiology and Statistics, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands
6. ⁶Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands

Correspondence: Dr AGJ van der Zee, E-mail: a.g.j.van.der.zee@og.umcg.nl

Revised 7 April 2008; Accepted 22 May 2008.

Abstract

Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in ovarian cancer but their prognostic value remains unclear. In this study, we investigated the expression and prognostic value of EGFR, EGFR variant III (EGFRvIII), HER-2/neu and important downstream signalling components in a large series of epithelial ovarian cancer patients. Immunohistochemical staining of EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) was performed in 232 primary tumours using the tissue microarray platform and related to clinicopathological characteristics and survival. In addition, EGFRvIII expression was determined in 45 tumours by RT–PCR. Our results show that negative PTEN immunostaining was associated with stage I/II disease (P=0.006), non-serous tumour type (P=0.042) and in multivariate analysis with a longer progression-free survival (P=0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P=0.011). Positive pAKT staining was associated with advanced-stage disease (P=0.006). Other proteins were expressed only at low levels, and were not associated with any clinicopathological parameter or survival. None of the tumours were positive for EGFRvIII. In conclusion, our results indicate that tumours showing negative PTEN staining could represent a subgroup of ovarian carcinomas with a relatively favourable prognosis.