Fractal dimension of chromatin is an independent prognostic factor for survival in melanoma.
BACKGROUND
Prognostic factors in malignant melanoma are currently based on clinical data and morphologic examination. Other prognostic features, however, which are not yet used in daily practice, might add important information and thus improve prognosis, treatment, and survival. Therefore a search for new markers is desirable. Previous studies have demonstrated that fractal characteristics of nuclear chromatin are of prognostic importance in neoplasias. We have therefore investigated whether the fractal dimension of nuclear chromatin measured in routine histological preparations of malignant melanomas could be a prognostic factor for survival.


METHODS
We examined 71 primary superficial spreading cutaneous melanoma specimens (thickness > or = 1 mm) from patients with a minimum follow up of 5 years. Nuclear area, form factor and fractal dimension of chromatin texture were obtained from digitalized images of hematoxylin-eosin stained tissue micro array sections. Clark's level, tumor thickness and mitotic rate were also determined.


RESULTS
The median follow-up was 104 months. Tumor thickness, Clark's level, mitotic rate, nuclear area and fractal dimension were significant risk factors in univariate Cox regressions. In the multivariate Cox regression, stratified for the presence or absence of metastases at diagnosis, only the Clark level and fractal dimension of the nuclear chromatin were included as independent prognostic factors in the final regression model.


CONCLUSIONS
In general, a more aggressive behaviour is usually found in genetically unstable neoplasias with a higher number of genetic or epigenetic changes, which on the other hand, provoke a more complex chromatin rearrangement. The increased nuclear fractal dimension found in the more aggressive melanomas is the mathematical equivalent of a higher complexity of the chromatin architecture. So, there is strong evidence that the fractal dimension of the nuclear chromatin texture is a new and promising variable in prognostic models of malignant melanomas.
Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil. drbedin@uol.com.br
Valcinir
V
Bedin
Randall L
RL
Adam
Bianca Cs
BC
de Sá
Gilles
G
Landman
Konradin
K
Metze
D014408:Biomarkers, Tumor / Q000235:genetics*; D053145:Cell Nucleus Size; D002843:Chromatin / Q000473:pathology*; D042002:Chromatin Assembly and Disassembly; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D005260:Female; D017709:Fractals; D006416:Hematoxylin; D006801:Humans; D007091:Image Processing, Computer-Assisted; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D008940:Mitotic Index; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D002843:Chromatin; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin