Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Abstract

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30 -1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients

“…[13][14][15][16] Ki-67 is present in all active phases of the cell cycle. We found that Ki-67 was complementary to p53 in identifying patients at risk for early post-transplant hepatocellular carcinoma recurrence.…”

“…Ki-67 expression was associated with prognosis in prostate, breast and lung cancer. [13][14][15][16] In contrast, an inverse association was observed with cervical cancer prognosis 17 and no association was found with prognosis in patients with colon and pancreatic cancer. 18,19 In a study of patients undergoing surgical resection for hepatocellular carcinoma, higher levels of expression of Ki-67 in tumor tissue were associated with higher tumor grade 20 and early disease recurrence.…”

Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines

“…Tumor proliferative activity, in general evaluated by Ki-67 expression, is a prognostic marker in different type of tumours included NSCLC and it is considered of potential interest in defining populations at high or low risk of recurrence [49]. No data are available about the possible correlation between high tumor proliferation and response to EGFR inhibitors.…”

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

“…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.…”