The heterogeneous distribution of monosomy 3 in uveal melanomas: implications for prognostication based on fine-needle aspiration biopsies.

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.

• Authors: Willem Maat, Ekaterina S Jordanova, Shama L van Zelderen-Bhola, Ed R Barthen, Hans W Wessels, Nicoline E Schalij-Delfos, Martine J Jager
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 131 Issue 1 Pg. 91-6 (Jan 2007) ISSN: 1543-2165 [Electronic] United States
• PMID: 17227129 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Biopsy, Fine-Needle
• Cell Nucleus (genetics)
• Chromosome Aberrations
• Chromosomes, Human, Pair 3 (genetics)
• Female
• Humans
• In Situ Hybridization, Fluorescence
• Karyotyping
• Male
• Melanoma (genetics, pathology)
• Middle Aged
• Monosomy (genetics, pathology)
• Paraffin Embedding
• Prognosis
• Tumor Cells, Cultured
• Uveal Neoplasms (genetics, pathology)