Prognostic significance of chromosome 3 alterations determined by microsatellite analysis in uveal melanoma: a long-term follow-up study

S Thomas,M Zeschnigk,C Pütter,D R Lohmann,S Weber,N Bornfeld

doi:10.1038/bjc.2012.54

S Thomas, M Zeschnigk + Show 4 more

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https://doi.org/10.1038/bjc.2012.54

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Abstract

Background:In uveal melanoma (UM), the most frequent primary intraocular tumour in adults, loss of one entire chromosome 3 (monosomy 3 (M3)) is observed in ∼50% of tumours and is significantly associated with metastatic disease. The strong association of metastatic disease with M3 offers the opportunity for molecular prognostic testing of UM patients.Methods:To re-evaluate M3 as prognostic marker in our clinical and laboratory setting and to determine the metastatic potential of rare tumours with partial M3, we performed a comprehensive study on 374 UM patients treated by enucleation in our clinic within 10 consecutive years, starting in 1998. Genotyping of all tumours was performed by microsatellite analysis.Results:Median follow-up time was 5.2 years. The disease-specific mortality rates (death by UM metastases) for tumours with disomy 3 (D3) and M3 were 13.2% and 75.1%, respectively. The disease-specific survival was worse when M3 was observed together with chromosome 8 alterations (P=0.020). Death of UM metastases was also observed in 12 patients (9%) with D3 tumours. The metastasising D3 tumours showed a larger basal tumour diameter (P=0.007), and were more frequently of mixed or epitheloid cell type (P<0.0001) than D3 tumours that did not metastasise. Mortality rate of tumours showing partial M3 (8.3%) was as low as that for tumours with D3.Conclusion:This shows that large tumours with disomy 3 have an increased risk to develop metastases. On the basis of these results, our clinic offers routine prognostic testing of UM patients by chromosome 3 typing.

Highlights

In uveal melanoma (UM), the most frequent primary intraocular tumour in adults, loss of one entire chromosome 3 (monosomy 3 (M3)) is observed in B50% of tumours and is significantly associated with metastatic disease
On the basis of the chromosome 3 microsatellite analysis (MSA) results, we classified the tumours into four groups: 128 tumours with disomy 3, 211 tumours with M3, 16 tumours with partial M3, and 19 tumours with allelic imbalance’ (AI)
We present long-term follow-up data on 374 UM patients that were all treated by enucleation

Summary

Introduction

In uveal melanoma (UM), the most frequent primary intraocular tumour in adults, loss of one entire chromosome 3 (monosomy 3 (M3)) is observed in B50% of tumours and is significantly associated with metastatic disease. To re-evaluate M3 as a prognostic marker in our clinical and laboratory setting, to determine the prognosis of patients with partial M3, and to better capture the prognostic value of an ambiguous chromosome 3 status, we performed a comprehensive retrospective study on 374 UM patients who were treated by enucleation in our clinic between January 1998 and December 2007, and for whom survival and genotyping data were available. We associated genetic and clinical data with death of patients caused by UM metastases.

Results

Conclusion