Abstract
Purpose: :
Fluorescence in situ hybridization (FISH) analyses on tumor sections and on isolated nuclei showed a frequent occurrence of tumor cell heterogeneity for monosomy 3 in uveal melanoma. This study was conducted to determine what percentage of uveal melanoma cells with monosomy 3 was related to patient mortality.
Methods: :
In order to determine the presence of monosomy 3, karyotyping and FISH were performed on cultured cells and FISH on isolated nuclei from 50 primary uveal melanomas. Clinical and pathological prognostic factors were assessed, and compared to 5-year survival data. Analyses were performed using Cox proportional hazards test, Log Rank analysis, sensitivity, specificity, and positive and negative likelihood ratios.
Results: :
Combined karyotyping and FISH on cultured cells showed monosomy 3 in 19 of 50 cases, while determination of the monosomy 3 status by FISH on isolated nuclei with a threshold of 5% assigned 31 of 50 cases to have monosomy 3, a threshold of 30% 26 of 50 cases, and a threshold of 50% aberrant nuclei 19 of 50 cases. However, even when monosomy 3 on isolated nuclei with a 5% cut-off value was used, a significant difference in 5-year survival was present (HR=15.5, P=.007), indicating that monosomy 3 in already >5% of tumor cells is related to death due to metastases.
Conclusions: :
In uveal melanoma, the presence of >5% of cells with monosomy 3 as determined by FISH on isolated nuclei is associated with the development of metastases within 5 years after enucleation.
Keywords: melanoma • tumors • oncology