Abstract
Purpose: :
To determine the relationship between immunohistochemical reactivity to five protein biomarkers (osteopontin, vimentin, keratin 8,18, LZTS1 and beta-catenin) and recognized clinical and histopathological prognostic factors for metastasis and death in archival specimens of primary choroidal and/or ciliary body melanoma.
Methods: :
Histopathological and immunohistochemical analysis of 118 cases of primary choroidal and/or ciliary body melanoma treated by primary enucleation at one center during the period May 1, 1999 through June 30, 2009. All tumors were classified histomorphologically in terms of melanoma cell type and vasculogenic mimicry pattern, and all were graded in terms of intensity of immunoreactivity to the five protein markers listed in the preceding paragraph. The cross-correlations between the variables were evaluated by chi-squared testing.
Results: :
After exclusions, our study group consisted of 82 specimens. At enucleation, patients ranged in age from 27 to 91 years (mean 62 years).The mean largest basal diameter was 14.5 mm (5 to 26 mm), and mean thickness was 8.5 mm (1.3 to 18 mm). 56 tumors (68.3%) were located in the choroid and 26 (31.7%) involved the ciliary body. 30 tumors (36.6%) were classified as spindle cell type, 31 (37.8%) as mixed cell type, 19 (23.2%) as epithelioid cell type, and 2 (2.4%) as necrotic. Extrascleral extension of microscopic or greater extent was identified in 10 (12.2%) tumors. As part of our immunohistochemical results 36.8% of specimens stained for keratin, 36.8% for osteopontin, 31.6% for β-catenin, 78.9% for vimentin, and 73.7% for LZTS1. The strongest relationship was between LZTS1 positivity and presence of metastasis (LZTS1 was positive in a 87.5% of specimens from patients with confirmed metastasis but only in 63.6% of specimens from patients who had not developed metastasis).Through available follow-up, 55 patients (67.1%) were alive without any evidence of cancer, 7 (8.5%) were dead of undetermined cause, and 20 (24.4%) were dead of confirmed metastatic melanoma.
Conclusions: :
Our study suggests that a combination of unfavorable clinical and histopathological factors including immunoexpression of molecular biomarkers related to metastatic behavior may allow better prognostication of metastasis than clinical and histomorphological factors alone.
Keywords: oncology • melanoma • immunohistochemistry