Boyd Alan S, Shakhtour Bashar, Shyr Yu
Department of Medicine (Dermatology), Vanderbilt University, Nashville, Tennessee, USA.
J Am Acad Dermatol. 2008 May;58(5):750-4. doi: 10.1016/j.jaad.2007.12.026. Epub 2008 Feb 4.
Minichromosome maintenance (MCM) proteins are a recently elucidated group of polypeptides intimately involved in DNA replication and appreciable only in cycling cells. In other organ systems their expression has proven more prognostically useful than cell proliferation markers such as Ki-67 and proliferating cell nuclear antigen. To date, the evaluation of MCM proteins in melanocytic neoplasms has not been undertaken.
We sought to determine whether MCM protein 2 (the most extensively evaluated of the MCM protein family) is present in melanocytes from benign nevi, dysplastic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases and, if so, whether there exists a significant difference in expression among the 3 groups.
Immunohistochemical staining for MCM 2 was performed on tissue sections from 10 benign nevi, dysplastic nevi, and primary cutaneous melanomas and from 5 cutaneous melanoma metastases. Approximately 200 cells were evaluated microscopically in 5 separate fields for each specimen and the number of positively staining nuclei was counted. After a percentage was calculated for each lesion, the data were pooled and statistically analyzed.
Melanocyte nuclear staining was readily visible microscopically. The percentage of positively staining nuclei in benign nevi (1.2%), dysplastic nevi (6.1%), primary cutaneous melanomas (49.1%), and cutaneous melanoma metastases (40.9%) was significantly different (P < .0001) among the 4 groups. Using paired comparisons, statistically significant differences were found between benign nevi and melanoma, dysplastic nevi and melanoma, benign nevi and cutaneous melanoma metastases, and dysplastic nevi and cutaneous melanoma metastases. There was no statistically significant difference between cutaneous melanoma metastases and primary cutaneous melanoma.
This is a small pilot study without blinded evaluation of the tissue sections and lacking correlation with patient clinical outcome or accepted histologic prognostic factors.
MCM protein expression appears to differ significantly in melanocytic neoplasms and potentially provides an additional tool for distinguishing benign tumors from their malignant counterparts. Further evaluation of this expression may prove useful in delineating the biologic behavior of these tumors and warrants additional research.
微小染色体维持(MCM)蛋白是最近阐明的一组多肽,与DNA复制密切相关,且仅在增殖细胞中可检测到。在其他器官系统中,它们的表达已被证明比细胞增殖标志物如Ki-67和增殖细胞核抗原在预后评估方面更具价值。迄今为止,尚未对黑素细胞肿瘤中的MCM蛋白进行评估。
我们试图确定MCM蛋白2(MCM蛋白家族中研究最广泛的一种)是否存在于良性痣、发育异常痣、原发性皮肤黑色素瘤和皮肤黑色素瘤转移灶的黑素细胞中,如果存在,这三组之间的表达是否存在显著差异。
对10例良性痣、发育异常痣和原发性皮肤黑色素瘤以及5例皮肤黑色素瘤转移灶的组织切片进行MCM 2免疫组化染色。在每个标本的5个不同视野中显微镜下评估约200个细胞,并计数阳性染色细胞核的数量。计算每个病变的百分比后,汇总数据并进行统计学分析。
显微镜下很容易看到黑素细胞核染色。良性痣(1.2%)、发育异常痣(6.1%)、原发性皮肤黑色素瘤(49.1%)和皮肤黑色素瘤转移灶(40.9%)中阳性染色细胞核的百分比在4组之间有显著差异(P <.0001)。通过配对比较,发现良性痣与黑色素瘤、发育异常痣与黑色素瘤、良性痣与皮肤黑色素瘤转移灶以及发育异常痣与皮肤黑色素瘤转移灶之间存在统计学显著差异。皮肤黑色素瘤转移灶与原发性皮肤黑色素瘤之间无统计学显著差异。
这是一项小型试点研究,未对组织切片进行盲法评估,且缺乏与患者临床结局或公认的组织学预后因素的相关性。
MCM蛋白表达在黑素细胞肿瘤中似乎有显著差异,可能为区分良性肿瘤与其恶性对应物提供了一种额外的工具。对这种表达的进一步评估可能有助于描绘这些肿瘤的生物学行为,值得进一步研究。