Harms Paul W, Hocker Thomas L, Zhao Lili, Chan May P, Andea Aleodor A, Wang Min, Harms Kelly L, Wang Michael L, Carskadon Shannon, Palanisamy Nallasivam, Fullen Douglas R
Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109.
Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109.
Hum Pathol. 2016 Dec;58:152-160. doi: 10.1016/j.humpath.2016.07.029. Epub 2016 Aug 26.
Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status. We analyzed a spectrum of benign (n=24), borderline (n=27), and malignant (n=19) spitzoid lesions for p16 protein expression by immunohistochemistry and CDKN2A copy number by FISH. Immunohistochemistry was evaluated by 2 scoring methods: H score and 2-tiered score (positive or negative for p16 loss). By immunohistochemistry, loss of p16 expression was not observed in Spitz nevi (0/24) but was seen in ASTs (7/27; 26%) and spitzoid melanomas (3/19; 16%). By H score, p16 expression was significantly higher in Spitz nevi relative to ASTs or spitzoid melanomas. Similarly, copy number aberrations of CDKN2A by FISH were absent in Spitz nevi but were found in 2 (9.5%) of 21 ASTs and 4 (33%) of 12 spitzoid melanomas. Our findings from this large cohort suggest that p16 aberrations are highly specific for borderline and malignant spitzoid neoplasms relative to Spitz nevi. Similar to ASTs, p16 loss in spitzoid melanomas may occur in the presence or absence of genomic CDKN2A loss.
梭形黑素细胞性病变，包括Spitz痣（良性）、梭形黑色素瘤（恶性）和交界性非典型Spitz肿瘤（ASTs），在准确诊断和预后方面常常带来挑战。对位于9号染色体短臂2区1带3亚带（9p21.3）上由CDKN2A基因编码的肿瘤抑制因子p16缺失情况进行评估，被认为有助于梭形黑素细胞性病变的评估。然而，关于p16免疫组化在梭形病变中的应用报道一直存在矛盾，很少有研究直接比较p16免疫组化与荧光原位杂交（FISH）检测CDKN2A基因状态的情况。我们通过免疫组化分析了一系列良性（n = 24）、交界性（n = 27）和恶性（n = 19）梭形病变的p16蛋白表达情况，并通过FISH分析了CDKN2A的拷贝数。免疫组化采用两种评分方法进行评估：H评分和两级评分（p16缺失为阳性或阴性）。通过免疫组化，在Spitz痣（0/24）中未观察到p16表达缺失，但在ASTs（7/27；26%）和梭形黑色素瘤（3/19；16%）中可见。通过H评分，Spitz痣中的p16表达明显高于ASTs或梭形黑色素瘤。同样，FISH检测显示Spitz痣中不存在CDKN2A的拷贝数异常，但在21例ASTs中有2例（9.5%）以及12例梭形黑色素瘤中有4例（33%）存在该异常。我们从这个大型队列研究中得出的结果表明，相对于Spitz痣，p16异常对于交界性和恶性梭形肿瘤具有高度特异性。与ASTs类似，梭形黑色素瘤中p16缺失可能在存在或不存在基因组CDKN2A缺失的情况下发生。
