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The Heterogeneous Distribution of Monosomy 3 in Uveal Melanomas: Implications for Prognostication Based on Fine-Needle Aspiration Biopsies

2007; American Medical Association; Volume: 131; Issue: 1 Linguagem: Inglês

10.5858/2007-131-91-thdomi

1543-2165

Willem Maat, Ekaterina S. Jordanova, Shama L. van Zelderen‐Bhola, E. R. Barthen, Hans W. Wessels, Nicoline E. Schalij‐Delfos, Martine J. Jager,

Cancer Genomics and Diagnostics

Abstract Context.—The detection of monosomy 3 in uveal melanomas has repeatedly been associated with adverse outcome. Fine-needle aspiration biopsy is being used to detect monosomy 3 in these tumors, based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor. Objective.—To study the distribution of monosomy 3 in primary uveal melanoma by fluorescence in situ hybridization (FISH). Design.—We studied 50 enucleated eyes with uveal melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA-specific probe for the centromere region of chromosome 3 on cultured tumor cells. In addition, the percentage of tumor cells with monosomy 3 was assessed by FISH on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH on regular histology sections of the paraffin-embedded tissue. Results.—Combining karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) of 50 tumors, whereas FISH on nuclei isolated from paraffin-embedded tissue showed 31 (62%) of 50 as having monosomy for chromosome 3. FISH analysis on paraffin sections showed tumor heterogeneity for copy number of chromosome 3 in at least 7 cases. Conclusions.—FISH analysis on paraffin sections shows that heterogeneity of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on nuclei isolated from paraffin-embedded tissue identifies a higher frequency of monosomy 3 than the traditional combination of karyotyping and FISH on cultured uveal melanoma cells. The practice of assigning patients to risk categories based on fine-needle aspiration biopsy samples from primary uveal melanoma may be subject to error based on the heterogeneous distribution of monosomy 3 in these tumors.