Effects Of Ki-67 Expression And Microvascular Invasion On Early Recurrence Of Primary Hepatocellular Carcinoma After Radical Hepatectomy

Background: Hepatocellular carcinoma(HCC)is the most important component of primary malignant tumors originating in the liver,which is alao one of the accepted tumors with high recurrence rate and mortality.Hepatectomy and liver transplantation have been widely considered as the first choice for the treatment of HCC.Advances in techniques of surgery have increased more patients’ access to surgical treatment,but the effect on long-term survival outcomes largely unsuccessfully.In particular,early recurrences(within 2 years after surgery)compared with advanced recurrence is associated with poor outcome after surgical resection.Microvascular invasion(MVI)is considered to be the determining factor leading to early recurrence and affecting long-term survival,which has become a the hot spot of the current research.Ki-67 is a kind of nuclcar-associated antigen which only expression in proliferating cell.It has been one of the widely used and well-studied marker associated with proliferation in human cancer.In HCC,the high expression of Ki-67 expression may foretell poor prognosis of tumors,but its clinical significance for early postoperative recurrence is unclear and the clinical application of Ki-67 is limited.At present,more studies are working to the analysis of other pathological and immune markers in conjunction with Ki-67.The hopeful stage was a better predictor of HCC prognosis.Objective: To investigate the effects of different Ki-67 expression levels and MVI status in HCC tissues on early recurrence after radical hepatectomy,in order to provide a basis for the identification of HCC patients with high recurrence risks.Methods: We collected the clinical and pathological date of 130 HCC patients from December 31,2015 to December 31,2018.All of them got radical hepatectomy in the Second Affiliated Hospital of Da Lian Medical University and were strictly followed up for the condition of recurrence within two years after hepatectomy.The expression of Ki-67 in the postoperative tumor specimen was quantitatively analyzed by immunohistochemistry(IHC).Afterward,all patients were subdivided into high expression and low expression group taking 30% of the median as the boundary.The correlations between Ki-67 and clinicopathological characteristics were analyzed in this study.Meanwhile,the risk factors affecting the early recurrence of HCC after radical hepatectomy were also analyzed.The effects of MVI and Ki-67 on early recurrence was determined by the analysis of DFS.All statistical analyses were performed with SPSS22.0,Kaplan-Meier method was used for univariate analysis,variables with statistical significance(P<0.05)were included in the multivariate Cox proportional hazard model.DFS curves(rates)were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.P < 0.05 was considered statistically significant.Results: In total,a number of 130 HCC patients met the inclusion criteria within 3years.Patients displayed low Ki-67 expression group(≤30%)with a total of 67 cases accounting for 51.5%;Patients displayed high Ki-67 expression group(> 30%)including 63 cases accounting for 48.5%.There were 75 cases(57.7%)in the MVI positive group,and 55 cases(42.3%)in the MVI negative group.Ki-67 expression were significantly correlated with tumor number(P=0.003),tumor size(P < 0.001),AFP(P=0.002)and HBs Ag(P < 0.001).Univariate analysis by Kaplan-Meier method showes that HBs Ag(P =0.001),satellite nodules(P =0.012),MVI(P =0.004),tumor number(P < 0.001),operation type(P =0.032),Ki-67(P < 0.001)have statistical significance on early recurrence after radical hepatectomy of HCC.Multivariate Cox proportional hazard model analysis: The number of tumors,MVI,Ki-67 expression and operation type are independent risk factors affecting the early recurrence.Patients with multiple tumors have a higher risk of early recurrence than those with single tumors(HR=2.123,95%CI:1.262~3.569),patients displayed high Ki-67 expression have a higher risk of early recurrence than those displayed low expression of Ki-67(HR=7.955,95%CI: 4.123~15.374)and patients with MVI have a higher risk of early recurrence than those without MVI(HR=1.874,95%CI:1.081~3.248).Anatomical versus non-anatomical resection is a protective factor of HCC after radical hepatectomy.(B:-0.988,HR=0.372,95%CI: 0.221~0.626).Disease-free survival analysis showes:The group with high Ki-67 expression(82.1%)is significantly lower than that of the group with low Ki-67 expression(20.6%)(P < 0.001).The MVI positive group(41.3%)is significantly lower than that of MVI negative group(67.3%)(P < 0.05).In the low-risk group(patients with low Ki-67 expression combined with MVI negative)(91.7%)is significantly better than that in the high-risk group(43.4%)(P < 0.001).Conclusion:1.Ki-67 expression is significantly correlated with tumor number,tumor size,AFP level and HBs Ag.2.Ki-67 expression,microvascular invasion,satellite nodules,HBs Ag,tumor number,and operation type are risk factors affecting the early recurrence after radical hepatectomy.3.High expression of Ki-67 、 microvascular invasion and multiple tumors are independent risk factors affecting the early recurrence after radical hepatectomy.However,anatomical resection is a protective factor for early recurrence.4.High expression of Ki-67 and microvascular invasion are high risk factors affecting the early recurrence after radical hepatectomy.