Dataset Information

Prognostic parameters in uveal melanoma and their association with BAP1 expression.

ABSTRACT: AIM:To determine whether BAP1 gene and protein expression associates with different prognostic parameters in uveal melanoma and whether BAP1 expression correctly identifies patients as being at risk for metastases, following enucleation of the primary tumour. METHODS:Thirty cases of uveal melanoma obtained by enucleation between 1999 and 2004 were analysed for a variety of prognostic markers, including histological characteristics, chromosome aberrations obtained by fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) analysis and gene expression profiling. These parameters were compared with BAP1 gene expression and BAP1 immunostaining. RESULTS:The presence of monosomy of chromosome 3 as identified by the different chromosome 3 tests showed significantly increased HRs (FISH on isolated nuclei cut-off 30%: HR 11.6, p=0.002; SNP analysis: HR 20.3, p=0.004) for death due to metastasis. The gene expression profile class 2, based on the 15-gene expression profile, similarly provided a significantly increased HR for a poor outcome (HR 8.5, p=0.005). Lower BAP1 gene expression and negative BAP1 immunostaining (50% of 28 tumours were immunonegative) were both associated with these markers for prognostication: FISH cut-off 30% monosomy 3 (BAP1 gene expression: p=0.037; BAP1 immunostaining: p=0.001), SNP-monosomy 3 (BAP1 gene expression: p=0.008; BAP1 immunostaining: p=0.002) and class 2 profile (BAP1 gene expression: p<0.001; BAP1 immunostaining: p=0.001) and were themselves associated with an increased risk of death due to metastasis (BAP1 gene expression dichotomised: HR 8.7, p=0.006; BAP1 immunostaining: HR 4.0, p=0.010). CONCLUSIONS:Loss of BAP1 expression associated well with all of the methods currently used for prognostication and was itself predictive of death due to metastasis in uveal melanoma after enucleation, thereby emphasising the importance of further research on the role of BAP1 in uveal melanoma.

SUBMITTER: van Essen TH

PROVIDER: S-EPMC4966163 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Prognostic parameters in uveal melanoma and their association with BAP1 expression.

van Essen T Huibertus TH van Pelt Sake I SI Versluis Mieke M Bronkhorst Inge H G IH van Duinen Sjoerd G SG Marinkovic Marina M Kroes Wilma G M WG Ruivenkamp Claudia A L CA Shukla Shruti S de Klein Annelies A Kiliç Emine E Harbour J William JW Luyten Gregorius P M GP van der Velden Pieter A PA Verdijk Rob M RM Jager Martine J MJ

The British journal of ophthalmology 20140821 12

<h4>Aim</h4>To determine whether BAP1 gene and protein expression associates with different prognostic parameters in uveal melanoma and whether BAP1 expression correctly identifies patients as being at risk for metastases, following enucleation of the primary tumour.<h4>Methods</h4>Thirty cases of uveal melanoma obtained by enucleation between 1999 and 2004 were analysed for a variety of prognostic markers, including histological characteristics, chromosome aberrations obtained by fluorescence i ...[more]

PMID: 25147369

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Project description:ImportanceUveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis.ObjectiveTo determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification.Design, setting, and participantsThis retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015.Main outcome and measuresProgression-free survival (PFS). The secondary outcome was overall survival.ResultsThe primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30-24.84; P?<?.001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02-1.26; P?=?.02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04-1.24; P?=?.005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort.Conclusions and relevanceClass 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy.

Dataset Information

Prognostic parameters in uveal melanoma and their association with BAP1 expression.

Publications

Prognostic parameters in uveal melanoma and their association with BAP1 expression.

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