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Background   CCND1  copy number increase is characteristic of acral melanoma and is useful in distinguishing benign and malignant acral melanocytic lesions. Increase of the gene copy number may result in protein overexpression. This raises the possibility that detection of high expression of cyclin D1 by immunohistochemistry (IHC) may be used as a surrogate for direct evaluation of increase in the  CCND1  gene copy number.    Methods  We examined increases in  CCND1  copy number with fluorescence in situ hybridization (FISH), and examined cyclin D1 protein expression with IHC in 61 acral melanomas.    Results  Using FISH, 29 acral melanomas (29/61, 47.5%) showed increase in the  CCND1  copy number, including 8 (8/61, 13.1%) which showed low-level increase in the  CCND1  copy number and 21 (21/61, 34.4%) with high-level increase in the  CCND1  copy number. By analysis of IHC, the median IHC score was 15% (range: 1–80%) in acral melanomas with no  CCND1  copy number alteration. In acral melanomas with low-level  CCND1  copy number increase, the median IHC score was 25% (range: 3–90%). In acral melanomas with high-level  CCND1  copy number increase, the median IHC score was 60% (range: 1–95%). Comparing FISH and IHC, cyclin D1 protein expression level has no corelation with the  CCND1  copy number in acral melanomas which have no  CCND1  copy number alteration and low-level  CCND1  copy number increase ( P  = 0.108). Cyclin D1 protein expression level correlated positively with  CCND1  copy number in acral melanomas with high-level  CCND1  copy number increase ( P  = 0.038). The sensitivity, specificity and positive predictive value of using cyclin D1 IHC to predict  CCND1  FISH result was 72.4, 62.5 and 63.6%. Increase in  CCND1  copy number was associated with Breslow thickness in invasive acral melanoma.    Conclusion  High-level increase in the  CCND1  copy number can induce high cyclin D1 protein expression in acral melanomas. However low-level increase and normal  CCND1  copy number have no obvious correlation with protein expression. Cyclin D1 IHC cannot serve as a surrogate for  CCND1  FISH in acral melanomas.

diagnostic pathology

CCND1 copy number increase and cyclin D1 expression in acral melanoma: a comparative study of fluorescence in situ hybridization and immunohistochemistry in a Chinese cohort