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Impressum
Membrane patterns and Factor VIII staining: prognostic significance in 100 cases of human uveal melanoma.
1Loeffler K. U., 2McLean. I. W.
1Department of Ophthalmology, University of Bonn, Germany, 2Division of Ophthalmic Pathology, AFIP, Washington, DC, USA
Objective: In uveal malignant melanomas, the patterns formed by
PAS stained membranes have been established as significant prognosticators.
Using 100 tumors with a known outcome, we have studied the interrelationships
of these patterns and their association with endothelial cells.
Methods: Cases were selected so that 49 of the patients died with
metastasis and all of the 51 remaining patients survived at least 9 years
without metastasis. A paraffin section from each tumor was bleached, stained
with PAS without hematoxylin and labeled with anti-Factor VIII (F8). All
sections were evaluated for the presence and amount of each of the patterns,
for the respective intensity of F8 labeling, and for which of the patterns
dominated. Five new variables (complexity within the straight and curved
hierarchies, F8 labeling, intensity of the dominant pattern, and independent
loops) were tested for prognostic significance. Statistical analysis was
performed using contingency tables and uni- and multivariate Cox regression.
Results: 99 sections could be evaluated. While Arcs was associated
with a favorable prognosis, Parallel with cross linking, Arcs with branching,
Loops and Networks were all associated with death. Analysis of the dominant
pattern revealed a highly significant association with outcome (X2 = 32.8,
Df = 7, p <0.0001). There was a favorable prognosis when the normal,
straight and arcs patterns dominated and an unfavorable prognosis when
the arcs with branching, isolated loops or networks were most prominent.
Two of the new variables (F8 and intensity of the dominant pattern of
PAS stained membranes) were not statistically significantly associated
(p > 0.05) with outcome. Most significant was the most complex pattern
within the curved hierarchy (X2 = 30.0) closely followed by networks (X2
= 27.2).
Conclusions: Our study confirmed the presence of networks in uveal
melanoma to be indicative of a poor prognosis. However, loops or networks
and the most complex pattern within the curved hierarchy, are as significant
predictors of outcome as networks. We also observed that the most complex
pattern does not have to dominate to have a prognostic effect and its
significance is unaffected by F8 staining.