Thörn M, Pontén F, Bergström R, Sparén P, Adami H O
Department of Surgery, University Hospital, Uppsala University, Sweden.
J Natl Cancer Inst. 1994 May 18;86(10):761-9. doi: 10.1093/jnci/86.10.761.
Previous malignant melanoma studies regarding prognostic factors have often selected their patients from hospitals. Unfortunately, most of these studies have had small numbers of patients, consisted of short-term data sets, omitted important factors, did not optimize histopathologic classification, had too short or inadequate follow-up, and did not test their predictive models.
Our study goals were to identify independent clinical and histopathologic determinants of survival in malignant melanoma, to analyze changes in prognostic value over follow-up time, and, finally to construct a prognostic index.
A random sample from the Swedish Cancer Registry of the records of 498 (246 men and 252 women) patients defined by gender, five 5-year time periods of diagnosis from 1960 through 1984, and five anatomic sites formed the cohort on whom data were analyzed by univariate analyses. Multivariate analyses were based on data on 476 patients with complete information about all variables. All patients in the cohort had complete follow-up through December 31, 1989. Clinical information was abstracted and recorded as: date of diagnosis, stage at diagnosis, sex, age, anatomic site of primary tumor, date of death, and cause of death. Histopathologic slides were re-examined and classified with regard to histogenetic type, level of invasion, tumor thickness, ulceration, vascular invasion, regression, lymphocytic reaction, pre-existing nevus, and cell type.
All variables, except pre-existing nevus and cell type, were significant predictors of survival. In the multivariate analyses including all variables, women still had a significant, 33% lower relative hazard than men. The prognosis was poor in the youngest age group. Patients with external ear, scalp-neck, and trunk-located melanoma had increasing relative hazard when all variables were included. Regional metastases and tumor thickness remained independent prognostic factors. No significant association between histogenetic type or level of invasion persisted. Patients whose tumors showed ulceration or vascular invasion had lower relative hazard when all variables were included. Level of invasion, tumor thickness, ulceration, and vascular invasion were significantly associated with the prognosis during both short- and long-term follow-up. The patients were subgrouped according to percentage fractions of their score on the prognostic index. Survival curves for these groups of patients were well separated, thus identifying patients with a low or high risk of death from malignant melanoma.
The present population-based study identifies independent clinical and histopathologic predictors of survival in cutaneous malignant melanoma and emphasizes the role of histopathologic characteristics such as tumor thickness, ulceration, and vascular invasion besides anatomic site.
以往关于恶性黑色素瘤预后因素的研究通常从医院选取患者。不幸的是，这些研究大多患者数量较少，数据集为短期数据，遗漏了重要因素，未优化组织病理学分类，随访时间过短或不充分，且未对其预测模型进行检验。
我们的研究目标是确定恶性黑色素瘤生存的独立临床和组织病理学决定因素，分析随访期间预后价值的变化，最后构建一个预后指数。
从瑞典癌症登记处随机抽取498例（246例男性和252例女性）患者的记录，这些患者按性别、1960年至1984年的五个5年诊断时间段以及五个解剖部位进行定义，构成队列，对其数据进行单变量分析。多变量分析基于476例具有所有变量完整信息的患者的数据。队列中的所有患者均随访至1989年12月31日。临床信息被提取并记录为：诊断日期、诊断分期、性别、年龄、原发肿瘤的解剖部位、死亡日期和死亡原因。对组织病理学切片重新进行检查，并根据组织发生类型、浸润深度、肿瘤厚度、溃疡、血管浸润、消退、淋巴细胞反应、既往痣和细胞类型进行分类。
除既往痣和细胞类型外，所有变量均为生存的显著预测因素。在包括所有变量的多变量分析中，女性的相对风险仍比男性显著低33%。最年轻年龄组的预后较差。当纳入所有变量时，外耳道、头皮 - 颈部和躯干部位黑色素瘤患者的相对风险增加。区域转移和肿瘤厚度仍然是独立的预后因素。组织发生类型或浸润深度之间无显著关联。当纳入所有变量时，肿瘤出现溃疡或血管浸润的患者相对风险较低。浸润深度、肿瘤厚度、溃疡和血管浸润在短期和长期随访中均与预后显著相关。根据预后指数得分的百分比对患者进行亚组划分。这些患者组的生存曲线有明显区分，从而识别出恶性黑色素瘤死亡风险低或高的患者。
本基于人群的研究确定了皮肤恶性黑色素瘤生存的独立临床和组织病理学预测因素，并强调了除解剖部位外肿瘤厚度、溃疡和血管浸润等组织病理学特征的作用。
