Department of Neuropathology, Institute of Pathology, University of Heidelberg, Germany.
Mod Pathol. 2010 Mar;23(3):413-9. doi: 10.1038/modpathol.2009.177. Epub 2010 Jan 15.
Recently, initial studies describing the use of multicolor fluorescence in situ hybridization (FISH) for classifying melanocytic skin lesions have been published demonstrating a high sensitivity and specificity in discriminating melanomas from nevi. However, the majority of these studies included neither histologically ambiguous lesions nor a clinical long-term follow up. This study was undertaken to validate a special multicolor FISH test in histologically ambiguous melanocytic skin lesions with known clinical long-term follow up. FISH was scored by three independent pathologists in a series of 22 melanocytic skin lesions, including 12 ambiguous cases using four probes targeting chromosome 6p25, centromere 6, 6q23, and 11q13. The FISH results were compared with array comparative genomic hybridization data and correlated to the clinical long-term follow up (mean: 65 months). Pair-wise comparison between the interpretations of the observers showed a moderate to substantial agreement (kappa 0.47-0.61). Comparing the FISH results with the clinical behavior reached an overall sensitivity of 60% and a specificity of 50% (chi(2)=0.25; P=0.61) for later development of metastases. Comparison of array comparative genomic hybridization data with FISH analyses did not yield significant results but array comparative genomic hybridization data demonstrated that melanocytic skin lesions with the development of metastases showed significantly more chromosomal aberrations (P<0.01) compared with melanocytic skin lesions without the development of metastases. The FISH technique with its present composition of locus-specific probes for RREB1/MYB and CCND1 did not achieve a clinically useful sensitivity and specificity. However, a reassessment of the probes and better standardization of the method may lead to a valuable diagnostic tool.
最近，描述使用多色荧光原位杂交（FISH）分类黑素细胞皮肤病变的初步研究已经发表，证明其在区分黑素瘤与痣方面具有很高的敏感性和特异性。然而，这些研究中的大多数都既没有包括组织学上有争议的病变，也没有包括临床长期随访。本研究旨在验证一种特殊的多色 FISH 检测方法在具有已知临床长期随访的组织学上有争议的黑素细胞皮肤病变中的有效性。FISH 由三位独立的病理学家在一系列 22 个黑素细胞皮肤病变中进行评分，包括 12 个使用针对染色体 6p25、着丝粒 6、6q23 和 11q13 的四个探针的有争议病例。FISH 结果与 array comparative genomic hybridization 数据进行了比较，并与临床长期随访（平均：65 个月）相关。观察者之间的解释的两两比较显示出中度至高度一致性（kappa 0.47-0.61）。将 FISH 结果与临床行为进行比较，总的敏感性为 60%，特异性为 50%（chi(2)=0.25；P=0.61），用于随后发生转移。array comparative genomic hybridization 数据与 FISH 分析的比较没有产生显著结果，但 array comparative genomic hybridization 数据表明，发生转移的黑素细胞皮肤病变显示出明显更多的染色体异常（P<0.01），与未发生转移的黑素细胞皮肤病变相比。目前由 RREB1/MYB 和 CCND1 的位点特异性探针组成的 FISH 技术没有达到临床上有用的敏感性和特异性。然而，对探针的重新评估和方法的更好标准化可能会导致一种有价值的诊断工具。
