Search

IMPORTANCE: Studies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but the prognosis of UMs with partial deletion of chromosome 3 remains to be defined. OBJECTIVE: To examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, assessed patients presenting with UMs with and without partial loss of chromosome 3 at a referral center. Data analysis was performed from September 1, 2017, to November 30, 2017. EXPOSURE: Uveal melanoma with or without partial loss of chromosome 3. MAIN OUTCOMES AND MEASURES: Metastasis-free survival and overall survival at 60 months. RESULTS: Of the 1088 consecutive comparative genomic hybridization arrays that were performed, 43 UMs (4.0%) in 43 patients (median age, 58 years [range, 12-79 years]; 22 [51%] female) carried partial deletions of chromosome 3. Median follow-up was 66 months (range, 1.2-126.2 months). Metastasis-free survival at 60 months was 33.6% (95% CI, 15.8%-71.4%) for UMs that carried a deletion of the BAP1 (BRCA1 associated protein 1) locus (BAP1del; 24 tumors) and 80.5% (95% CI, 64.8%-100%) for UMs without the loss of the BAP1 locus (BAP1 normal [BAP1nl]; 19 tumors) (log-rank P = .001). Overall survival at 60 months was 64.5% (95% CI, 43.5%-95.8%) in the BAP1del group vs 84.1% (95% CI, 69.0%-100%) in the BAP1nl group (log-rank P < .001). In these 43 cases, metastasis-free survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 70.0% (95% CI, 50.5%-96.9%) for UMs that carried 1 of these alterations, and 12.5% (95% CI, 2.1%-73.7%) for those that carried both (log-rank P < .001). Similarly, overall survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 80.8% (95% CI, 63.3%-100%) for UMs that carried 1 of these alterations, and 46.7% (95% CI, 23.3%-93.6%) for those that carried both (log-rank P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.

Importance The influence of ocular treatment of choroidal melanoma on survival has yet to be elucidated. Objective To determine whether treatment of choroidal melanoma influences survival by correlating age at death, cause of death, age at treatment, and survival predictors. Design, Setting, and Participants Prospective cohort study performed at the Liverpool Ocular Oncology Centre, a supraregional, tertiary referral service in England. We included 3072 patients treated for choroidal melanoma from January 15, 1993, through November 23, 2012, and who reside in the mainland United Kingdom. Exposures A diagnosis of choroidal melanoma (ie, any uveal melanoma involving the choroid). Main Outcomes and Measures Largest basal tumor diameter, tumor thickness, TNM stage, ciliary body involvement, extraocular spread, melanoma cytomorphological findings, closed connective tissue loops, mitotic count, chromosome 3 loss, chromosome 6p gain, chromosome 8q gain, age at treatment, age at death, and cause of death. Results The largest basal tumor diameter correlated with all survival predictors except for chromosome 6p gain. Older age at treatment correlated with ciliary body involvement, extraocular spread, largest basal tumor diameter, tumor thickness, TNM stage, epithelioid cells, chromosome 3 loss, and chromosome 8q gain. A total of 1005 patients had died by the close of the study. The cause of death was metastatic disease due to uveal melanoma in 561 patients. Among the 561 patients, survival time after treatment correlated with sex, basal tumor diameter, ciliary body involvement, extraocular spread, TNM stage, closed loops, and mitotic count. In this group of patients, none of the survival predictors correlated with age at death except for mitotic count, which showed a weak correlation. All survival predictors correlated with an increased likelihood of metastatic melanoma as the cause of death. Conclusions and Relevance Patients who are younger at the time of treatment tend to have a smaller, less extensive tumor with a lower degree of malignancy. A tentative explanation for these findings is that ocular treatment prevents tumor growth, dedifferentiation, and metastatic disease in some patients, especially those with a smaller tumor.