Monosomy 3 in uveal melanoma: correlation with clinical and histologic predictors of survival.
OBJECTIVE
To correlate monosomy 3 in uveal melanoma with clinical and histologic prognostic variables and death caused by metastatic disease.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Scholes
Andrea G M
AG
Unit of Ophthalmology, Department of Medicine, The University of Liverpool, Liverpool, United Kingdom.
Damato
Bertil E
BE
Nunn
Janice
J
Hiscott
Paul
P
Grierson
Ian
I
Field
John K
JK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009006:Monosomy; D016133:Polymerase Chain Reaction; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
D004273:DNA, Neoplasm