Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Pathology. 2017 Dec;49(7):740-749. doi: 10.1016/j.pathol.2017.08.006. Epub 2017 Oct 14.
Acral melanoma is associated with outcomes which are more unfavourable than those of other melanoma subtypes, and acral melanoma has higher mortality. However, histological distinction of acral melanoma from acral naevi may be difficult. Fluorescence in situ hybridisation (FISH) targeting specific genes has been used as an ancillary method for differential diagnosis of melanocytic tumours, but most previous studies have focused on non-acral lesions which may have genetic alterations different from acral lesions. We evaluated use of multi-site FISH in the diagnosis of acral melanoma in a series of 82 acral melanocytic tumours. Two probe groups were applied. Probe set 1 involved a 4-probe FISH targeting 6p25 (RREB1), CEP6 (centromere 6), 6q23 (MYB) and 11q13 (CCND1). Probe set 2 involved a 3-probe FISH targeting 8q24 (MYC), 9p21 (CDKN2A) and CEP9 (centromere 9). In 44 primary acral melanomas, sensitivity was 70.5% (31/44) using probe set 1 alone, and 59.1% (26/44) using probe set 2 alone. When both probe sets were combined, sensitivity increased to 88.6% (39/44). The frequency of each gene alteration was as follows: MYC gain in 54.5% cases (24/44), RREB1 gain in 52.3% cases (23/44), CCND1 gain in 45.4% cases (20/44), MYB loss relative to CEP6 in 25.0% cases (11/44), and CDKN2A homozygous deletion in 20.5% cases (9/44). For lesions with both in situ and invasive disease, FISH findings in these two components were similar. No gene alterations were detected in any of 36 benign acral naevi. In this study FISH exhibited sensitivity and specificity in diagnosis of acral melanoma which allows its application as an auxiliary diagnostic test in acral melanocytic tumours.
肢端黑素瘤的预后比其他黑素瘤亚型差，死亡率更高。然而，肢端黑素瘤与肢端痣的组织学鉴别可能具有挑战性。荧光原位杂交（FISH）针对特定基因已被用作黑素瘤肿瘤鉴别诊断的辅助方法，但大多数先前的研究都集中在非肢端病变上，这些病变的遗传改变可能与肢端病变不同。我们评估了在一系列 82 例肢端黑素细胞肿瘤中使用多部位 FISH 诊断肢端黑素瘤的情况。应用了两组探针。探针组 1 包含一个针对 6p25（RREB1）、CEP6（着丝粒 6）、6q23（MYB）和 11q13（CCND1）的 4 探针 FISH 探针组。探针组 2 包含一个针对 8q24（MYC）、9p21（CDKN2A）和 CEP9（着丝粒 9）的 3 探针 FISH 探针组。在 44 例原发性肢端黑素瘤中，单独使用探针组 1 的敏感性为 70.5%（31/44），单独使用探针组 2 的敏感性为 59.1%（26/44）。当两个探针组联合使用时，敏感性增加到 88.6%（39/44）。每个基因改变的频率如下：MYC 增益 54.5%（24/44），RREB1 增益 52.3%（23/44），CCND1 增益 45.4%（20/44），MYB 相对于 CEP6 的缺失 25.0%（11/44），CDKN2A 纯合缺失 20.5%（9/44）。对于原位和侵袭性疾病均存在的病变，这两种成分的 FISH 结果相似。在 36 例良性肢端痣中均未检测到基因改变。在这项研究中，FISH 在诊断肢端黑素瘤中表现出敏感性和特异性，使其可作为肢端黑素细胞肿瘤的辅助诊断检测方法。
