BACKGROUND: P53, EGFR and HER-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance. METHODS: Published studies that investigated the association between p53, EGFR and HER-2/neu status and survival were identified. Meta-analysis was performed using a DerSimonian -Laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis. RESULTS: A total of 62 studies were included for p53, 15 for EGFR and 20 for HER-2/neu. P53, EGFR and HER-2/neu status had a modest effect on overall survival (pooled HR 1.47, 95% CI 1.33 -1.61 for p53; HR 1.65, 95% CI 1.25 -2.19 for EGFR and HR 1.67, 95% CI 1.34 -2.08 for HER-2/neu). Meta-regression analysis for p53 showed that FIGO stage distribution influenced study outcome. For EGFR and HER-2/neu, considerable publication bias was present. CONCLUSIONS: Although p53, EGFR and HER-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies.

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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 ¼ 0.006), non-serous tumour type (P ¼ 0.042) and in multivariate analysis with a longer progression-free survival (P ¼ 0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P ¼ 0.011). Positive pAKT staining was associated with advanced-stage disease (P ¼ 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.