Augmented expression of Ki-67 is correlated with clinicopathological characteristics and prognosis for lung cancer patients: an up-dated systematic review and meta-analysis with 108 studies and 14,732 patients

Abstract

BackgroundLung cancer ranks as the leading cause of cancer-related deaths worldwide and we performed this meta-analysis to investigate eligible studies and determine the prognostic effect of Ki-67.MethodsIn total, 108 studies in 95 articles with 14,732 patients were found to be eligible, of which 96 studies reported on overall survival (OS) and 19 studies reported on disease-free survival (DFS) with relation to Ki-67 expression in lung cancer patients.ResultsThe pooled hazard ratio (HR) indicated that a high Ki-67 level could be a valuable prognostic factor for lung cancer (HR = 1.122 for OS, P < 0.001 and HR = 1.894 for DFS, P < 0.001). Subsequently, the results revealed that a high Ki-67 level was significantly associated with clinical parameters of lung cancer including age (odd ratio, OR = 1.246 for older patients, P = 0.018), gender (OR = 1.874 for males, P < 0.001) and smoking status (OR = 3.087 for smokers, P < 0.001). Additionally, significant positive correlations were found between Ki-67 overexpression and poorer differentiation (OR = 1.993, P = 0.003), larger tumor size (OR = 1.436, P = 0.003), and higher pathologic stages (OR = 1.867 for III-IV, P < 0.001). Furthermore, high expression of Ki-67 was found to be a valuable predictive factor for lymph node metastasis positive (OR = 1.653, P < 0.001) and advanced TNM stages (OR = 1.497 for stage III-IV, P = 0.024). Finally, no publication bias was detected in any of the analyses.ConclusionsThis study highlights that the high expression of Ki-67 is clinically relevant in terms of the prognostic and clinicopathological characteristics for lung cancer. Nevertheless, more prospective well-designed studies are warranted to validate these findings.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0843-7) contains supplementary material, which is available to authorized users.

Cutoff of 25% for Ki67 expression is a good classification tool for prognosis in colorectal cancer in the AJCC‑8 stratification

“…How to grade Ki67 expression remains therefore an open question. A 20% cutoff has been reported (38). Nonetheless, a previous meta-analysis assessing various cut-off levels of Ki67 in regards to prognosis suggested a visual cut-off >25% to provide a higher discriminatory power in mortality risk compared with the remaining cut-off points evaluated (39).…”

“…Indeed, head-to-head comparisons between scores from automated and pathologist-based techniques in terms of prognostic value have been rarely reported, and discrepant findings in breast cancer have been obtained (35)(36)(37). Previous reports (38,39) discussed the role of Ki67 expression in lung and breast cancers, examining ways to define the cutoff of Ki67 expression. Similar questions remain for CRC.…”

Ki-67/MKI67 as a Predictive Biomarker for Clinical Outcome in Gastric Cancer Patients: an Updated Meta-analysis and Systematic Review involving 53 Studies and 7078 Patients

“…A large number of studies have reported the clinical and prognostic value of Ki-67/MKI67 in various malignancies, such as breast cancer 9, cervical cancer 10, glioma 11, colorectal cancer 12 and hepatocellular carcinoma 13. Our research group previously conducted systematic meta-analyses to explore the prognostic role of Ki-67/MKI67 in lung cancer 14, hepatocellular carcinoma 13, cervical cancer 15, glioma 16 and colorectal cancer 17 and found that Ki-67/MIB-1 could be an independent prognostic biomarker in these types of carcinoma.…”

A method to obtain reproducible Ki‐67 indices in lung adenocarcinoma

“…The Ki‐67 labelling index has been examined in several types of malignant tumours. Previous studies reported the random counting of cells in representative areas and in hot‐spots (where several tumour cells express Ki‐67) 5,16,23 . Regarding LADC, tumour cells were predominantly counted in representative areas and successfully demonstrated the prognostic benefits of the Ki‐67 labelling index 5,17,23 .…”

“…The proliferative activity of neoplastic cells, measured by the Ki‐67 labelling index, is one of the most useful diagnostic and prognostic markers in patients with malignant tumours 1–5 . Previous studies have confirmed its benefit and proposed cut‐off values to differentially diagnose malignant from benign tumours and assess their outcomes 6–12 …”