Assessment of the extent of unpublished studies in prognostic factor research: a systematic review of p53 immunohistochemistry in bladder cancer as an example.

OBJECTIVES: When study groups fail to publish their results, a subsequent systematic review may come to incorrect conclusions when combining information only from published studies. p53 expression measured by immunohistochemistry is a potential prognostic factor in bladder cancer. Although numerous studies have been conducted, its role is still under debate. The assumption that unpublished studies too harbour evidence on this research topic leads to the question about the attributable effect when adding this information and comparing it with published data. Thus, the aim was to identify published and unpublished studies and to explore their differences potentially affecting the conclusion on its function as a prognostic biomarker. DESIGN: Systematic review of published and unpublished studies assessing p53 in bladder cancer in Germany between 1993 and 2007. RESULTS: The systematic search revealed 16 studies of which 11 (69%) have been published and 5 (31%) have not. Key reason for not publishing the results was a loss of interest of the investigators. There were no obviously larger differences between published and unpublished studies. However, a meaningful meta-analysis was not possible mainly due to the poor (ie, incomplete) reporting of study results. CONCLUSIONS: Within this well-defined population of studies, we could provide empirical evidence for the failure of study groups to publish their results that was mainly caused by loss of interest. This fact may be coresponsible for the role of p53 as a prognostic factor still being unclear. We consider p53 and the restriction to studies in Germany as a specific example, but the critical issues are probably similar for other prognostic factors and other countries.

Assessment of breast cancer vascularisation by Doppler ultrasound as a prognostic factor of survival.

Tumor growth and metastasis in breast cancer are correlated to neoangiogenesis, which became a potential candidate as a prognostic factor in this tumor type. Several studies have used immunohistochemical staining to count microvessel density as a marker of neoangiogenesis. This hospital-based retrospective pilot study measured vascularisation of early breast cancer by Doppler ultrasound and determined its value as a prognostic factor of overall survival in 147 women. The number of tumor related arteries were detected by color-coded Doppler ultrasound. We identified < or =10 tumor arteries and >10 tumor arteries in 117 and 30 women, respectively. Only weak correlation was found between the number of tumor arteries and established clinicopathological parameters such as tumor size (r=0.25) and lymph node involvement (r=0.13). In an univariate analysis, the strongest predictors of overall survival were number of tumor arteries [relative risk (RR) 4.60 (1.96-10.78)], positive axillary lymph nodes [RR 4.48 (1.59-12.60)] and angioinvasion [RR 4.26 (1.93-9.37)]. These three parameters were also found to be independent predictors of overall survival in a multivariate analysis [RR 3.21 (1.13-9.10) for positive lymph nodes; RR 2.69 (1.33-5.41) for number of tumor arteries; RR 2.84 (1.27-6.34) for angioinvasion]. Tumor vascularisation detected by Doppler ultrasound appears to be an independent predictor of overall survival in women with early breast cancer.