Abstract
BACKGROUND—Previous work has highlighted the prognostic importance of patterns of periodic acid Schiff (PAS) staining (the Folberg patterns) in uveal melanoma. These patterns have been ascribed to blood vessels but the patterns are different from those seen with other staining techniques for blood vessels. It has recently been shown that microvessel density is the dominant prognostic factor in uveal melanoma. This study reinvestigates the nature and significance of the PAS patterns. METHODS—The PAS patterns were compared with the patterns seen with conventional connective tissue stains and with the patterns seen in sections stained for the presence of blood vessels (by immunohistochemistry for factor VIII related antigen). The PAS patterns were determined on a panel of 117 cases of uveal melanoma. The prognostic significance of each of these patterns was determined and, as more than one pattern can exist in a tumour, principal components analysis was performed to determine the number of underlying factors. RESULTS—Comparison of the PAS patterns with other stains demonstrates that they are based on connective tissue including fibrovascular tissue. Five of the nine PAS patterns carried prognostic significance on univariate analysis. Principal components analysis suggested that these patterns represented three underlying factors, which were tentatively identified as representing disordered growth (factor 1), emergence of rapidly growing subclones (factor 2), and section orientation (factor 3). CONCLUSIONS—The PAS patterns are based on fibrovascular tissue and can be ascribed to three underlying factors. The first two of these factors carried prognostic significance and the first (disordered growth) retained independent prognostic significance in a multivariate Cox model which included microvessel density and tumour size.
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Figure 1 .
(A) A PAS section showing an `area of silence' (area 1) bordering an `area of normal vasculature' (area 2). (B) A corresponding section stained for F8, showing the presence of numerous small blood vessels in the `area of silence'. Magnification × 60.
Figure 2 .
A PAS stained section (A) showing the presence of a `vascular loop, with a corresponding section (B) stained with F8 showing no loops. Magnification × 60.
Figure 3 .
A section corresponding to those in Figure 2, stained with Harris's haematoxylin and viewed with a fluorescent microscope with the appropriate filters for fluorescein viewing. It shows an autofluorescent pattern similar to that seen with the PAS reaction. Magnification × 70.
Figure 4 .
Kaplan-Meier graph for the first summary score.
Selected References
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