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The p16-Ki-67-HMB45 Immunohistochemistry Scoring System is Highly Concordant With the Fluorescent In Situ Hybridization Test to Differentiate Between Melanocytic Nevi and Melanomas

Uguen, Arnaud, MD, PhD*,†,‡; Uguen, Marie, MD, MSc; Guibourg, Briac, BM; Talagas, Matthieu, MD†,‡,§; Marcorelles, Pascale, MD, PhD†,‡,§; De Braekeleer, Marc, MD, PhD*,‡,∥

Applied Immunohistochemistry & Molecular Morphology: July 2018 - Volume 26 - Issue 6 - p 361–367
doi: 10.1097/PAI.0000000000000428
Research Articles

The treatment of melanoma requires early diagnosis and extensive surgical removal of the primary tumor. The differential diagnosis between a melanoma and a nevus is sometimes difficult from a histopathologic point of view and could require ancillary diagnostic tools. Recently, both fluorescent in situ hybridization (FISH) and p16-Ki67-HMB45 combined immunohistochemistry have been proposed as examples of ancillary diagnostic methods to help classify melanocytic tumors as benign or malignant. In this study, we compare FISH and p16-Ki-67-HMB45 immunohistochemistry in a set of melanomas and nevi. A total of 101 formalin-fixed and paraffin-embedded tumor samples (44 melanomas and 57 nevi) were analyzed using FISH for chromosomes 6, 8, 9, and 11 and p16-Ki-67-HMB45 immunohistochemistry. Any chromosomal imbalances and/or a p16-Ki-67-HMB45 immunohistochemistry combined score of 4 or higher were considered to reflect a “favor” malignant tumor. Using FISH, 42 out of 44 melanomas presented at least 1 chromosomal imbalance, whereas 2 melanomas and all nevi did not. Each melanoma, including 6 challenging tumors, had a p16-Ki-67-HMB45 immunohistochemistry combined score of 4 or higher and every nevus had a score inferior to 4. This reflects an excellent strength of agreement between FISH, immunohistochemistry, and definitive histopathologic diagnosis in our tumor set. We conclude that both FISH and p16-Ki67-HMB45 combined immunohistochemistry are valuable ancillary diagnostic tools to help pathologists classify melanocytic tumors as nevi or melanomas.

*Inserm, U1078

Brest University Hospital, Department of Pathology

European University of Brittany

§Brest Medecine School

Brest University Hospital, Department of Cytogenetics and Reproduction Biology, Brest, France

Supported by the associations “Vaincre Le Mélanome” and the “Omnium group.”

The authors declare no conflict of interest.

Reprints: Arnaud Uguen, MD, Department of Pathology, University Hospital Morvan, 5, Avenue Foch, 29609 Brest, France (e-mail:

Received April 15, 2016

Accepted June 24, 2016

Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved.