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Mehmet Dogrusoz, Wilma G. M. Kroes, Sjoerd van Duinen, Carien L. Creutzberg, Mieke Versluis, Jaco C. Bleeker, Marina Marinkovic, Gregorius P M Luyten, Martine J Jager; Irradiation enhances chromosomal aberrations in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5343.
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© ARVO (1962-2015); The Authors (2016-present)
We wondered whether uveal melanoma (UM) would show different chromosomal aberrations after previous irradiation. Chromosome analysis of UM was performed by karyotyping and fluorescence in situ hybridization (FISH). We determined the spectrum of chromosomal aberrations in a retrospective cohort of enucleated UM, some of which had previously undergone brachytherapy or proton beam irradiation. Furthermore, we analyzed which tumor features determined success or failure of karyotyping and FISH.
Material from 327 UM-containing enucleated eyes was submitted for karyotyping, while FISH analysis for chromosome 3 was performed in 240 samples. 36 UM had previously undergone irradiation. The outcome of karyotyping was studied, and the success rate of both techniques was evaluated and compared to clinicopathologic characteristics of the tumor and to prior irradiation treatment.
Karyotypes showed that aberrations occur in all chromosomes, with chromosomes 1, 3, 6, 8, 13, 15, 16 and Y being altered in at least 15% of the tumors. Aberrations were more common in previously irradiated tumors, compared to primarily enucleated cases, and reached significance for chromosomes 5 and 13 (p=0.004 and p=0.04, respectively, Table 1).<br /> Karyotyping was successful in 79% of primarily enucleated tumors, but only in 25% of previously irradiated tumors (p<0.001). In primarily enucleated cases, both a large tumor prominence (p=0.004) and a high mitotic count (p=0.007) were associated with successful karyotyping. In previously irradiated tumors, this was only true for a high mitotic count (p=0.03). FISH analysis for monosomy 3 failed significantly more often in irradiated tumors as well (p=0.04), and was more often successful when primarily enucleated tumors contained epithelioid cells (p=0.002); in previously irradiated cases, FISH analysis was more often successful in tumors with a large diameter (p=0.015) and prominence (p=0.001), and a high mitotic count (p=0.019).
Karyotyping demonstrated that all chromosomes in UM can be aberrant, with an increased frequency after irradiation. Prior irradiation and histopathologic features characteristic of low tumor aggressiveness were associated with both unsuccessful karyotyping and FISH. The frequent lack of success in irradiated tumors emphasizes the shortcomings of these techniques and shows the relevance of taking biopsies for chromosomal testing prior to irradiation treatment.
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