title: Can immunohistochemical markers and mitotic rate improve prognostic precision in patients with primary melanoma?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Fachklinik Hornheide, Münster, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ostmeier
authors.forename: B
authors.initials: B
authors.lastname: Fuchs
authors.forename: F
authors.initials: F
authors.lastname: Otto
authors.forename: R
authors.initials: R
authors.lastname: Mawick
authors.forename: A
authors.initials: A
authors.lastname: Lippold
authors.forename: V
authors.initials: V
authors.lastname: Krieg
authors.forename: L
authors.initials: L
authors.lastname: Suter
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000737:chemistry*; D008938:Mitosis / Q000502:physiology*; D015999:Multivariate Analysis; D011379:Prognosis; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor