Monosomy 3 in uveal melanoma: correlation with clinical and histologic predictors of survival.

Abstract

To correlate monosomy 3 in uveal melanoma with clinical and histologic prognostic variables and death caused by metastatic disease. Loss of heterozygosity (LOH) on chromosome 3 was investigated by PCR-based microsatellite analysis in 105 tumors and related to large basal tumor diameter (LBD), ciliary body (CB) involvement, tumor cell type, periodic acid-Schiff (PAS)-positive loops, and death related to metastatic disease. A model relating monosomy 3 to these was created with forward-stepwise logistic regression and used to derive a prognostic index. Monosomy 3 occurred in 54 (51%) tumors and regional chromosome 3 LOH in another six (6%) tumors. Monosomy 3 was associated with epithelioid cells (chi(2) test, P < 0.001), PAS-positive loops (chi(2), P = 0.001), LBD (Mann-Whitney test, P = 0.002), CB involvement (chi(2) test, P = 0.008), and metastasis-related death (log rank analysis, P = 0.0003). The regression coefficients indicated that epithelioid histology was 15 times as influential with each millimeter of increase in LBD. A prognostic score was derived: one point for each LBD category (<7.4, 7.5-12.4, 12.5-17.4, and >17.4 mm) and three points for epithelioid histology. The prevalence of monosomy 3 increased with score, from 0% in 18 tumors scoring less than 4 to 95% in 21 tumors scoring 7. Monosomy 3 correlates with survival but can be predicted only in patients with large epithelioid tumors. The absence of monosomy 3 is predictable only in patients who have small, spindle-cell tumors. In most patients, prediction of monosomy 3 according to tumor size and histology is unreliable.