探讨Ki-67增殖指数在套细胞淋巴瘤组织分型与预后中的临界值

Cut-off value of Ki-67 labeling index in the histological typing and prognosis of mantle cell lymphoma

目的探讨Ki-67增殖指数在套细胞淋巴瘤(mantle cell lymphoma,MCL)组织分型(经典型和侵袭性变异型)及在经典型MCL预后中的临界值。方法回顾性分析334例MCL患者的临床病理资料,对Ki-67增殖指数进行定量评估和相关性统计分析。结果 334例MCL中,男女比为2. 9∶1,平均年龄(60. 6±9. 6)岁,中位年龄61岁(25～83岁)。经Mann Whitney U检验,经典型和侵袭性变异型中Ki-67增殖指数的平均值差异有显著性(24. 8%±12. 5%、60. 1%±11. 7%,P <0. 001)。四格表诊断试验分析Ki-67增殖指数> 50%是预测侵袭性变异型MCL的重要因素(χ2=167. 551,P <0. 001)。Ki-67增殖指数临界值为50%时诊断为侵袭变异型有高灵敏度(83. 9%)和特异度(95. 4%)。ROC曲线法分析经典型MCL最佳的诊断临界值为40%,敏感度为93. 2%,特异度为95. 0%,ROC曲线下面积(area under the cure,AUC)最大(AUC=0. 980,P <0. 001,95%CI为0. 967～0. 993)。237例MCL(70. 9%)获得随访,中位随访时间26个月(3～108个月)。当临界值为20%时,经典型MCL生存曲线呈明显不同(P <0. 05)。结论 Ki-67增殖指数临界值<40%是诊断经典型MCL的可靠指标,> 50%提示可能是侵袭性变异型;在经典型MCL患者中临界值20%有临床意义。

Purpose To investigate the cut-off value of Ki-67 labeling index(LI)in the histological typing(classic and invasive variant)of mantle cell lymphoma(MCL)and prognosis of classic MCL.Methods The clinicopathological data of 334 patients with MCL were analyzed retrospectively,and the quantitative evaluation and statistical analysis of Ki-67 LI were carried out.Results Among the 334 patients with MCL,the male and female ratio was 2.9∶1,the average age was(60.6±9.6)years,the median age was 61 years(range 25 to 83 years).The differences in the average value(24.8%±12.5%vs 60.1%±11.7%,P<0.001)of Ki-67 LI in the classic and aggressive variant were statistically significant by Mann Whitney U test.According to the analysis of four lattice diagnostic tests,Ki-67 LI>50%was an important factor(χ2=167.551,P<0.001)in predicting aggressive variant.When the cut-off value of Ki-67 LI was 50%,it had the greatest sensitivity(83.9%)and specificity(95.4%)in the diagnosis of the aggressive variant.Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of classic MCL was 40%,the sensitivity was 93.2%,the specificity was 95.0%,and the area under curve(AUC)was the largest(AUC=0.980,P<0.001,95%CI for 0.967-0.993).Two hundred and thirty-seven patients had median follow-up time of 26 months(range:3-108 months).When the cut-off value was 20%,it was statistically significant(P<0.05)in the classic MCL patients.Conclusion The cut-off value of Ki-67 LI less than 40%is a reliable indicator for the diagnosis of classic MCL,and more than 50%of Ki-67 LI suggests that it may be an aggressive variant.The cut-off value for 20%in patients with classic MCL has clinical significance.