PMID- 34225728 OWN - NLM STAT- MEDLINE DCOM- 20211230 LR - 20231213 IS - 1746-1596 (Electronic) IS - 1746-1596 (Linking) VI - 16 IP - 1 DP - 2021 Jul 5 TI - 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. PG - 60 LID - 10.1186/s13000-021-01116-0 [doi] LID - 60 AB - 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. FAU - Liu, Jianying AU - Liu J AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Yu, Wenjuan AU - Yu W AD - Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China. FAU - Gao, Fei AU - Gao F AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Qi, Shuangshuang AU - Qi S AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Du, Juan AU - Du J AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Ma, Xiaolong AU - Ma X AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Zheng, Jie AU - Zheng J AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. FAU - Su, Jing AU - Su J AUID- ORCID: 0000-0002-4810-6096 AD - Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. sujing@bjmu.edu.cn. LA - eng GR - 81802245/National Natural Science Foundation of China/ PT - Comparative Study PT - Journal Article DEP - 20210705 PL - England TA - Diagn Pathol JT - Diagnostic pathology JID - 101251558 RN - 0 (CCND1 protein, human) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - China MH - Cohort Studies MH - Cyclin D1/genetics/*metabolism MH - DNA Copy Number Variations/*genetics MH - Female MH - Gene Amplification/genetics MH - Gene Dosage MH - Humans MH - *Immunohistochemistry/methods MH - *In Situ Hybridization, Fluorescence/methods MH - Male MH - Melanoma/*genetics MH - Middle Aged MH - Skin Neoplasms/*genetics MH - Melanoma, Cutaneous Malignant PMC - PMC8259423 OTO - NOTNLM OT - Acral melanoma OT - CCND1 (cyclin D1) OT - Gene copy number increase OT - Protein expression COIS- The authors declare that they have no competing interests. EDAT- 2021/07/07 06:00 MHDA- 2021/12/31 06:00 PMCR- 2021/07/05 CRDT- 2021/07/06 05:38 PHST- 2021/02/14 00:00 [received] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/07/06 05:38 [entrez] PHST- 2021/07/07 06:00 [pubmed] PHST- 2021/12/31 06:00 [medline] PHST- 2021/07/05 00:00 [pmc-release] AID - 10.1186/s13000-021-01116-0 [pii] AID - 1116 [pii] AID - 10.1186/s13000-021-01116-0 [doi] PST - epublish SO - Diagn Pathol. 2021 Jul 5;16(1):60. doi: 10.1186/s13000-021-01116-0.