Radiation Treatment Affects Chromosome Testing in Uveal Melanoma

• Published in: Investigative ophthalmology & visual science 2015-09, Vol.56 (10), p.5956-5964
• Main Authors: Dogrusöz, Mehmet, Kroes, Wilma G M, van Duinen, Sjoerd G, Creutzberg, Carien L, Versluis, Mieke, Bleeker, Jaco C, Marinkovic, Marina, Luyten, Gregorius P M, Jager, Martine J
• Format: Article
• Language: English
• Subjects: Chromosome Disorders - diagnosis; Chromosome Disorders - etiology; Chromosome Disorders - genetics; Chromosomes, Human - radiation effects; Chromosomes, Human, Pair 3; Female; Genetic Testing; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Melanoma - diagnosis; Melanoma - genetics; Melanoma - radiotherapy; Middle Aged; Retrospective Studies; Uveal Neoplasms - diagnosis; Uveal Neoplasms - genetics; Uveal Neoplasms - radiotherapy
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.15-17092

The purpose of this study was to determine whether radiation treatment induces chromosomal aberrations in uveal melanoma (UM) and to evaluate which tumor features determine success of karyotyping and FISH. Material from 327 UM-containing enucleated eyes was submitted for karyotyping, while FISH for chromosome 3 was performed in 248 samples. Thirty-six UMs had previously undergone irradiation. Karyotypes were analyzed, and the success rate of karyotyping/FISH was evaluated and compared with clinicopathologic tumor characteristics and prior irradiation. Aberrations were observed 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 and more complex in previously irradiated tumors (significant for chromosomes 5 [P = 0.004] and 13 [P = 0.04]). Karyotyping and FISH failed significantly more often in irradiated tumors (both P < 0.001). In nonirradiated cases, successful karyotyping was related to a large tumor prominence (P = 0.004) and a high mitotic count (P = 0.007). The success of FISH in these tumors was not associated with any of the studied parameters. In irradiated tumors, karyotyping succeeded more frequently in cases with a high mitotic count (P = 0.03), whereas FISH was more often successful in tumors with a high mitotic count (P = 0.001), a large diameter (P = 0.009) and large prominence (P = 0.008). Karyotyping and FISH are more often successful in UMs with features characteristic of high tumor aggressiveness, whereas prior irradiation leads to multiple chromosome aberrations and to unsuccessful tests. It will be interesting to determine whether other techniques can provide reliable information on the chromosome status of previously irradiated UMs.