Tucker Margaret A, Fraser Mary C, Goldstein Alisa M, Struewing Jeffery P, King Mary A, Crawford John T, Chiazze Ellen A, Zametkin Deborah P, Fontaine Laura S, Clark Wallace H
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892-7236, USA.
Cancer. 2002 Jun 15;94(12):3192-209. doi: 10.1002/cncr.10605.
Few long-term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes.
Thirty-three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups.
All the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early.
The melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families.
基于黑素瘤风险增加的家族的突变状态，关于黑素细胞病变的长期临床和组织学数据很少。在本研究中，作者描述了黑素瘤风险增加且CDKN2A、CDK4存在不同种系突变或尚未鉴定出基因的家族中，发育异常痣和黑素瘤随时间变化的临床和组织学特征。
对33个有超过2名在世成员患浸润性黑素瘤的家族进行临床评估，并进行长达25年的前瞻性随访。所有参与者均由美国国立卫生研究院临床中心或当地诊所的同一研究团队进行评估。在获得知情同意后，对家庭成员（n = 844）进行检查并拍照。采集血液进行基因研究；对CDKN2A和CDK4进行基因分型。作为临床评估的一部分，拍摄黑素细胞病变的系列照片。当切除黑素细胞病变时，对组织学进行复查。为六类病变和三个突变组选择代表性照片和显微照片。
所有家族均发现有成员患有发育异常痣和黑素瘤；17个家族的CDKN2A有突变，2个家族的CDK4有突变，14个家族未发现这两个基因有突变。大多数发育异常痣要么保持稳定，要么消退；很少有变化到应引起黑素瘤担忧的程度。通过仔细监测，可以早期发现黑素瘤。
在研究家族中发现的黑素瘤和发育异常痣似乎不因家族中鉴定出的突变类型而有所不同。
