Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation

Abstract

Background/aims: Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The efficiency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival.

Methods: 33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by Kaplan-Meier survival curves.

Results: Of the 33 tumours analysed, 16 showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The difference in survival between the two groups was highly significant (p<0.0001).

Conclusion: The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and efficient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

Figure 1

Three captured FISH images. (A) A disaggregated uveal melanoma tissue sample with cells showing a normal complement of two target hybridisation signals for each chromosome, thus signifying no genetic imbalance. (B) An image showing cells with monosomy 3 (red target hybridisation signals, rhodamine) and trisomy 8 (green target hybridisation signals, FITC), thus signifying genetic imbalance. (C) Another image also showing genetic imbalance but with a normal complement of two hybridisation signals for chromosome 3 but with four hybridisation signals for chromosome 8.

Figure 2

Kaplan-Meier survival curve for deaths due to liver metastases.

Figure 3

Kaplan-Meier survival curve for all deaths.