PMID- 27698849 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 12 IP - 4 DP - 2016 Oct TI - Fluorescence in situ hybridization testing of chromosomes 6, 8, 9 and 11 in melanocytic tumors is difficult to automate and reveals tumor heterogeneity in melanomas. PG - 2734-2741 AB - Malignant melanomas may be difficult to differentiate from benign nevi on the basis of histology. Contrary to nevi, the majority of melanomas harbor chromosomal imbalances. Comparative genomic hybridization-based and fluorescence in situ hybridization (FISH) tests can help differentiating malignant from benign tumors. In the present study, eight-bacterial artificial chromosome (BAC) probes targeting chromosomes 6, 8, 9 and 11 were tested by FISH, and compared with a commercial four-color FISH probe set targeting chromosomes 6 and 11 in a first set of 62 tissue microarray-included melanocytic tumors (47 melanomas and 15 nevi). A second set of 108 tumors (70 melanomas and 38 nevi) was analyzed with the eight-probes kit, and manual counting was compared with the newly developed automated FISH signals counting and with semi-quantitative visual detection of chromosomal imbalances. Intra-tumor heterogeneity was also evaluated in 12 melanomas and 10 patients with paired melanoma samples. Testing the tumors from the first set with the commercial kit and the eight-probes test permitted to correctly identify 45/47 and 47/47 melanomas, respectively. In the second tumor set, 65/70 malignant tumors presented at least one chromosomal imbalance, whereas none was detected in the nevi. The agreement between manual and automated signals counting was better in good-quality FISH slides compared with poor-quality slides. Semi-quantitative visual appreciation of chromosomal imbalances also reached strong agreement with exact manual counting. In addition, a frequent cytogenetic heterogeneity within melanomas and between paired tumors was noticed in patients with metastatic melanomas. To conclude, FISH testing targeting chromosomes 6, 8, 9 and 11 enabled to differentiate the majority of melanomas from nevi but was difficult to automate. Tumor cytogenetic heterogeneity was frequent and could impair FISH testing. FAU - Uguen, Arnaud AU - Uguen A AD - Inserm, U1078, F-29609 Brest, France; Department of Pathology, Brest University Hospital, F-29220 Brest, France; European University of Brittany, F-29220 Brest, France. FAU - Uguen, Marie AU - Uguen M AD - Department of Pathology, Brest University Hospital, F-29220 Brest, France. FAU - Talagas, Matthieu AU - Talagas M AD - Department of Pathology, Brest University Hospital, F-29220 Brest, France; European University of Brittany, F-29220 Brest, France; EA4685, Brest Medical School, F-29220 Brest, France. FAU - Gobin, Eric AU - Gobin E AD - Department of Pathology, Brest University Hospital, F-29220 Brest, France. FAU - Marcorelles, Pascale AU - Marcorelles P AD - Department of Pathology, Brest University Hospital, F-29220 Brest, France; European University of Brittany, F-29220 Brest, France; EA4685, Brest Medical School, F-29220 Brest, France. FAU - De Braekeleer, Marc AU - De Braekeleer M AD - Inserm, U1078, F-29609 Brest, France; European University of Brittany, F-29220 Brest, France; Department of Cytogenetics and Reproduction Biology, Brest University Hospital, F-29220 Brest, France. LA - eng PT - Journal Article DEP - 20160803 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC5038458 OTO - NOTNLM OT - chromosome OT - fluorescence in situ hybridization OT - melanoma OT - nevus OT - tumor heterogeneity EDAT- 2016/10/05 06:00 MHDA- 2016/10/05 06:01 PMCR- 2016/08/03 CRDT- 2016/10/05 06:00 PHST- 2015/11/22 00:00 [received] PHST- 2016/06/16 00:00 [accepted] PHST- 2016/10/05 06:00 [entrez] PHST- 2016/10/05 06:00 [pubmed] PHST- 2016/10/05 06:01 [medline] PHST- 2016/08/03 00:00 [pmc-release] AID - OL-0-0-4949 [pii] AID - 10.3892/ol.2016.4949 [doi] PST - ppublish SO - Oncol Lett. 2016 Oct;12(4):2734-2741. doi: 10.3892/ol.2016.4949. Epub 2016 Aug 3.