The diagnostic and prognostic values of Ki-67/MIB-1 expression in thyroid cancer: a meta-analysis with 6,051 cases

Background: Growing evidence has demonstrated that Ki-67/MIB-1 has an effect on the clinical progression and prognosis in cancers. However, the diagnostic and prognostic values of Ki-67/MIB-1 in thyroid cancer remain unclear. Materials and methods: The meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were retrieved from PubMed, EBSCO, EMBASE, ISI Web of Science, China National Knowledge Infrastructure, WanFang and Chinese VIP databases. MetaDiSc and STATA12.0 were used to analyze the meta-analysis. Fixed-effect analysis and random-effect analysis were applied to pool the relative ratio based on heterogeneity in this meta-analysis. Results: In the meta-analysis, 51 eligible studies were included. The pooled sensitivity of Ki-67/MIB-1 was 0.61 (95% confidence interval [CI]: 0.59-0.63) and specificity was 0.75 (95% CI: 0.74-0.77) in thyroid cancer. The pooled positive likelihood ratio was 3.19 (95% CI: 2.30-4.42) and negative likelihood ratio was 0.43 (95% CI: 0.35-0.54). In the diagnosis of thyroid cancer, the pooled diagnostic odds ratio of Ki-67/MIB-1 was 8.54 (95% CI: 5.03-14.49). The area under the symmetric receiver operating characteristic curve was 0.804 (standard error = 0.031). Our results showed that there were statistical associations between Ki-67/MIB-1 and age (odds ratio [OR] = 1.71, 95% CI: 1.14-2.57, P=0.010), tumor size (OR = 1.86, 95% CI: 1.17-2.96, P=0.008), lymph node metastasis (OR = 2.49, 95% CI: 1.42-4.39, P=0.002), metastasis status (OR = 6.96, 95% CI: 2.46-19.69, P < 0.001), tumor node metastasis stage (OR = 6.56, 95% CI: 3.80-11.34, P < 0.001) and extrathyroid extension (OR = 1.91, 95% CI: 1.27-2.87, P=0.002). Furthermore, thyroid cancer patients with a high level of Ki-67/MIB-1 had a worse disease-free survival as compared to patients with a low level of Ki-67/MIB-1 (hazard ratio = 5.19, 95% CI: 3.18-8.46, P < 0.001). Also, Ki-67/MIB-1 was found to be associated with increased risk of mortality (hazard ratio = 3.56, 95% CI: 1.17-10.83, P=0.025). Conclusion: Our results demonstrated that Ki-67/MIB-1 might act as a potential factor in diagnosing thyroid cancer in Chinese. Also, the meta-analysis indicated that Ki-67/MIB-1 might have an effect on prognosis in non-Chinese thyroid cancer patients.