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.
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.
Authors: Long V Ly; Inge H G Bronkhorst; Els van Beelen; Johannes Vrolijk; Andrew W Taylor; Mieke Versluis; Gregorius P M Luyten; Martine J Jager Journal: Invest Ophthalmol Vis Sci Date: 2010-06-10 Impact factor: 4.799
Authors: Mohamed H Abdel-Rahman; Benjamin N Christopher; Mohammed F Faramawi; Khaled Said-Ahmed; Carol Cole; Andrew McFaddin; Abhik Ray-Chaudhury; Nyla Heerema; Frederick H Davidorf Journal: Mod Pathol Date: 2011-04-15 Impact factor: 7.842
Authors: Benjamin N Christopher; Colleen M Cebulla; Paul E Wakely; Frederick H Davidorf; Mohamed H Abdel-Rahman Journal: Exp Eye Res Date: 2011-09-17 Impact factor: 3.467
Authors: T Huibertus van Essen; Sake I van Pelt; Mieke Versluis; Inge H G Bronkhorst; Sjoerd G van Duinen; Marina Marinkovic; Wilma G M Kroes; Claudia A L Ruivenkamp; Shruti Shukla; Annelies de Klein; Emine Kiliç; J William Harbour; Gregorius P M Luyten; Pieter A van der Velden; Rob M Verdijk; Martine J Jager Journal: Br J Ophthalmol Date: 2014-08-21 Impact factor: 4.638