Diaz Alba, Puig-Butillé Joan Anton, Valera Alexandra, Muñoz Concha, Costa Dolors, Garcia-Herrera Adriana, Carrera Cristina, Sole Francesc, Malvehy Josep, Puig Susana, Alos Llucia
Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
Department of Biochemical and Molecular Genetics, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), the Carlos III Institute of Health (ISCIII), Barcelona, Spain.
J Mol Diagn. 2014 Mar;16(2):198-206. doi: 10.1016/j.jmoldx.2013.10.009. Epub 2013 Dec 27.
The study of specific chromosomal loci through fluorescence in situ hybridization (FISH) is useful in differential diagnosis of melanocytic tumors. However, sensitivity rates vary, probably because of molecular heterogeneity. Acral lentiginous melanomas are characterized by copy number gains of small genomic regions, including CCND1, TERT, and AURKA. In a series of 58 acral melanocytic lesions, we explored the value of a four-color FISH probe, used in addition to determining MYC gene status, and assessed the potential diagnostic usefulness of newly developed probes targeting TERT and AURKA. Moreover, we tested CCND1, TERT, and AURKA protein expression by immunohistochemistry. The four-color FISH probe detected 85.3% of melanomas and 29.4% of TERT and AURKA copy number gains. Sensitivity was 97% (confidence interval 95%, 82.9% to 99.8%) for the combined results of all probes. No MYC copy number gains were detected. No nevi showed aberrations. Immunohistochemistry revealed a higher percentage of cells positive for CCND1, TERT, and AURKA protein in melanomas than in nevi (P ≤ 0.001). A significant correlation between gene copy number gain and protein expression was found for CCND1 (P = 0.015). Our results indicate that addition of specific FISH probes to the current probe could improve sensitivity for the diagnosis of acral melanomas. Further studies in larger numbers of cases are needed to validate these results.
通过荧光原位杂交（FISH）对特定染色体位点进行研究，在黑素细胞肿瘤的鉴别诊断中很有用。然而，灵敏度有所不同，这可能是由于分子异质性所致。肢端雀斑样痣性黑素瘤的特征是小基因组区域存在拷贝数增加，包括CCND1、TERT和AURKA。在一系列58例肢端黑素细胞病变中，我们探索了一种四色FISH探针的价值，除了确定MYC基因状态外还使用该探针，并评估了针对TERT和AURKA的新开发探针的潜在诊断效用。此外，我们通过免疫组织化学检测了CCND1、TERT和AURKA蛋白表达。四色FISH探针检测到85.3%的黑素瘤以及29.4%的TERT和AURKA拷贝数增加。所有探针的联合结果灵敏度为97%（置信区间95%，82.9%至99.8%）。未检测到MYC拷贝数增加。痣未显示异常。免疫组织化学显示，黑素瘤中CCND1、TERT和AURKA蛋白阳性细胞的百分比高于痣（P≤0.001）。发现CCND1的基因拷贝数增加与蛋白表达之间存在显著相关性（P = 0.015）。我们的结果表明，在当前探针中添加特定FISH探针可提高肢端黑素瘤诊断的灵敏度。需要对更多病例进行进一步研究以验证这些结果。
