Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis

Abstract

The role of p53, as a prognostic factor for survival in lung cancer, is controversial and the purpose of the present systematic review of the literature is to determine this effect.Published studies were identified with the objective to aggregate the available survival results after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to deal with p53 assessment in lung cancer (primary site) only, and to provide a survival comparison according to the p53 status.Among the 74 eligible papers, 30 identified p53 abnormalities as a univariate statistically significant poor prognostic factor and 56 provided sufficient data to allow survival results aggregation. There was no significant difference between the trials that either showed or did not show a prognostic effect of p53 according to the methodological score or to the laboratory technique used. The studies were categorized by histology, disease stage, treatment and laboratory technique. Combined hazard ratios suggested that an abnormal p53 status had an unfavourable impact on survival: in any stage nonsmall cell lung cancer (NSCLC) the mean (95% confidence interval) was 1.44 (1.20-1.72) (number of studies included in the subgroup was 11), 1.50 (1.32-1.70) in stages I-II NSCLC (n=19), 1.68 (1.23-2.29) in stages I-IIIB NSCLC (n=5), 1.68 (1.30-2.18) in stages III-IV NSCLC (n=9), 1.48 (1.29-1.70) in surgically resected NSCLC (n=20), 1.37 (1.02-1.85) in squamous cell carcinoma (n=9), 2.24 (1.70-2.95) in adenocarcinoma (n=9), 1.57 (1.28-1.91) for a positive immunohistochemistry with antibody 1801 (n=8), 1.25 (1.09-1.43) for a positive immunohistochemistry with antibody DO-7 (n=16), and 1.65 (1.35-2.00) for an abnormal molecular biology test (n=13). Data were insufficient to determine the prognostic value of p53 in small cell lung cancer.In each subgroup of nonsmall cell lung cancer, p53 abnormal status was shown to be associated with a poorer survival prognosis. Lung cancer is the most common cause of cancer death in industrialized countries and its incidence is steadily increasing in females and in many European countries. Despite improvements in diagnosis and therapy, the overall 5-yr survival is still 15%.Some independent prognostic factors have been identified for predicting survival and helping in the management of patients with lung cancer [1]. They include: for small cell lung cancer (SCLC), extent of disease and performance status (PS) [2]; for resectable nonsmall cell lung cancer (NSCLC), PS, tumour, node, metastasis (TNM) stage, and age [3]; for advanced NSCLC, PS, TNM stage, age, sex and weight loss [4,5]. Among biological factors, white blood cell count, serum lactate dehydrogenase level, angiogenesis and factors reflecting proliferative state have been shown to significantly predict outcome [6,7].Recent progresses in molecular biology have allowed for the extension of the research on prognostic factors to the analysis of proteins and genes involved in cancer...

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

“…Consensual agreement on the scores attributed to each item for each trial was obtained during meetings where the participation of many readers was a guarantee for the correct interpretation of the articles. The scoring system used in this literature review has already been described in one of our prior systematic reviews (Steels et al, 2001). The overall score assessed many dimensions of methodology, grouped in four main categories: the scientific design, the description of the laboratory methods used to quantify MVC, the generalisability of the results and the analysis of the study data.…”

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

“…We performed a methodological assessment of the studies to avoid some selection biases (more detailed reports of significant trials), as we performed in prior studies about biological prognostic factors in lung cancer (Steels et al, 2001). The absence of a detectable difference in quality score between significant and non-significant studies, and between evaluable and non-evaluable studies, encourages us to perform a quantitative aggregation (meta-analysis) of the results of the individual trials.…”

“…However, this approach does not prevent all potential biases. Publication bias, choice of language, selection of fully published studies only, method of extrapolation of HR, validity of a meta-analysis based on systematic review of the literature as compared with those based on individual data were already discussed in our previous papers (Steels et al, 2001). …”

“…The participation of many readers was a guarantee for the correct interpretation of the articles. The methodological evaluation was scored according to the European Lung Cancer Working Party (ELCWP) scale previously published (Steels et al, 2001) and applied in other meta-analyses (Delmotte et al, 2002;Meert et al, 2002aMeert et al, , b, 2003Martin et al, 2003Martin et al, , 2004Mascaux et al, 2005a). Each item was assessed using an ordinal scale (possible values: 2, 1, 0).…”

“…In order to clarify the prognostic impact of other biological factors in lung cancer, our group has performed systematic reviews of the literature with meta-analyses. It allowed us to show that VEGF (Delmotte et al, 2002), microvessel density (Meert et al, 2002b), EGFR (Meert et al, 2002a), HER-2/Neu , Ki-67 (Martin et al, 2004), K-Ras (Mascaux et al, 2005a) and p53 (Steels et al, 2001) have a negative impact on survival, whereas Bcl-2 is associated with a favourable survival effect, at least when studying their impact in univariate analysis.…”