Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, San Francisco, California.
Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Cancer. 2020 Nov 1;126(21):4717-4725. doi: 10.1002/cncr.33088. Epub 2020 Aug 11.
Mitotic rate is a strong, independent prognostic factor in patients with melanoma. However, incorporating it into the melanoma staging system has proved challenging.
The prognostic impact of mitotic rate was assessed in a melanoma cohort comprising 5050 patients from 2 geographically distinct populations. Computer-generated cut points for mitotic rate were constructed to determine its impact on melanoma-associated survival using Kaplan-Meier and multivariate regression analyses. The impact of mitotic rate also was assessed in randomly split training and validation sets.
Mitotic rate had a nonlinear impact on survival, as evidenced by unequally spaced cut points. An index incorporating these cut points that was constructed from one population produced significantly more accurate predictions of survival in the other population than using the entire scale of mitotic rate. An index constructed from the combined cohort was found to be independently predictive of survival, with an impact comparable to that of ulceration. Optimal high-versus-low cut points for mitotic rate were generated separately for each T category (<2 mitoses/mm vs ≥2 mitoses/mm for T1 melanoma, <4 mitoses/mm vs ≥4 mitoses/mm for T2 melanoma, <6 mitoses/mm vs ≥6/mitoses/mm for T3 melanoma, and <7 mitoses/mm vs ≥7 mitoses/mm for T4 melanoma). Using Kaplan-Meier analysis, elevated mitotic rate was found to have an impact on survival comparable to that of ulceration within each T category. Application of the index for mitotic rate that was constructed from the training data set demonstrated an independent impact in the validation data set, with a significance similar to that of ulceration.
The results of the current study demonstrated the comparable prognostic impact of mitotic rate and ulceration, providing support for its reincorporation into the T category.
有丝分裂率是黑色素瘤患者的一个强有力的独立预后因素。然而，将其纳入黑色素瘤分期系统一直具有挑战性。
对来自两个地理上不同人群的 5050 例黑色素瘤患者队列进行了有丝分裂率的预后影响评估。使用 Kaplan-Meier 和多变量回归分析构建了计算机生成的有丝分裂率切点，以确定其对黑色素瘤相关生存的影响。在随机划分的训练集和验证集中也评估了有丝分裂率的影响。
有丝分裂率对生存的影响呈非线性，证据是切点不均匀分布。从一个人群构建的包含这些切点的指数在另一个人群中对生存的预测比使用有丝分裂率的整个范围更为准确。从联合队列构建的指数被发现可独立预测生存，其影响与溃疡相当。分别为每个 T 类别生成了最佳的高-低有丝分裂率切点（T1 黑色素瘤<2 个有丝分裂/毫米与≥2 个有丝分裂/毫米，T2 黑色素瘤<4 个有丝分裂/毫米与≥4 个有丝分裂/毫米，T3 黑色素瘤<6 个有丝分裂/毫米与≥6 个有丝分裂/毫米，T4 黑色素瘤<7 个有丝分裂/毫米与≥7 个有丝分裂/毫米）。使用 Kaplan-Meier 分析，在每个 T 类别中，升高的有丝分裂率对生存的影响与溃疡相当。应用从训练数据集构建的有丝分裂率指数在验证数据集中显示出独立的影响，其显著性与溃疡相似。
当前研究的结果表明有丝分裂率和溃疡的预后影响相当，支持将其重新纳入 T 类别。
