Ostmeier H, Fuchs B, Otto F, Mawick R, Lippold A, Krieg V, Suter L
Fachklinik Hornheide, Münster, Germany.
Cancer. 1999 Jun 1;85(11):2391-9. doi: 10.1002/(sici)1097-0142(19990601)85:11<2391::aid-cncr14>3.0.co;2-i.
In addition to tumor thickness, several other prognostic parameters have been identified in primary human melanomas. Some are available readily (localization, gender, age, and ulceration). Others must be evaluated with a moderate or even substantial amount of work (mitoses and immunohistochemical markers). This study was undertaken to determine whether this extra effort is justified because it actually improves the precision of prognostic statements.
Immunohistologic markers were determined on frozen sections from 691 biopsies of human melanomas with the immunoperoxidase method. Univariate and multivariate Cox regression analyses were performed with metastases and with death as endpoints.
Fifteen parameters were related to disease free survival in univariate Cox regression analysis: tumor thickness, ulceration, localization, gender, age, mitoses, and the immunohistochemical markers very late antigen (VLA)-2, human leukocyte antigen (HLA)-ABC, HLA-DR, NKI-beteb, Mel 14, intercellular adhesion molecule (ICAM-1), K-1-2, G-7-E2, and H-2-4-7. Three of the easily available parameters exhibited independent significance in multivariate Cox regression analysis: tumor thickness, ulceration, and localization. If mitotic rate was included in this model, then it had independent prognostic significance but ulceration was no longer significant. However, the model that included tumor thickness, localization, and ulceration had a slightly higher overall chi-square test score, indicating a better performance compared with thickness, localization, and mitoses. The model that included tumor thickness, localization, and mitoses could not be improved by any of the immunohistochemical markers in this study.
Nine immunohistochemical markers with established prognostic significance for primary human melanoma were not found to improve a prognostic model that included tumor thickness, localization, and mitoses. If mitoses was replaced by ulceration, then the model performed slightly better, although ulceration was not significant in the presence of mitoses.
除肿瘤厚度外,在原发性人类黑色素瘤中还确定了其他几个预后参数。有些参数很容易获得(定位、性别、年龄和溃疡形成情况)。其他参数则必须通过适度甚至大量的工作来评估(有丝分裂和免疫组化标记物)。本研究旨在确定这种额外的努力是否合理,因为它实际上提高了预后判断的准确性。
采用免疫过氧化物酶法对691例人类黑色素瘤活检的冰冻切片进行免疫组织学标记物检测。以转移和死亡为终点进行单变量和多变量Cox回归分析。
在单变量Cox回归分析中,有15个参数与无病生存期相关:肿瘤厚度、溃疡形成情况、定位、性别、年龄、有丝分裂以及免疫组化标记物极迟抗原(VLA)-2、人类白细胞抗原(HLA)-ABC、HLA-DR、NKI-beteb、Mel 14、细胞间黏附分子(ICAM)-1、K-1-2、G-7-E2和H-2-4-7。在多变量Cox回归分析中,三个容易获得的参数具有独立的显著性:肿瘤厚度、溃疡形成情况和定位。如果将有丝分裂率纳入该模型,则它具有独立的预后意义,但溃疡形成情况不再具有显著性。然而,包含肿瘤厚度、定位和溃疡形成情况的模型总体卡方检验得分略高,表明与包含厚度、定位和有丝分裂的模型相比性能更好。在本研究中,包含肿瘤厚度、定位和有丝分裂的模型无法通过任何免疫组化标记物得到改善。
未发现9种对原发性人类黑色素瘤具有既定预后意义的免疫组化标记物能改善包含肿瘤厚度、定位和有丝分裂的预后模型。如果将有丝分裂替换为溃疡形成情况,则模型性能略有改善,尽管在有有丝分裂的情况下溃疡形成情况不具有显著性。