Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions

Paul W. Harms*, Thomas L. Hocker, Lili Zhao, May P. Chan, Aleodor A. Andea, Min Wang, Kelly L. Harms, Michael L. Wang, Shannon Carskadon, Nallasivam Palanisamy, Douglas R. Fullen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status. We analyzed a spectrum of benign (n = 24), borderline (n = 27), and malignant (n = 19) spitzoid lesions for p16 protein expression by immunohistochemistry and CDKN2A copy number by FISH. Immunohistochemistry was evaluated by 2 scoring methods: H score and 2-tiered score (positive or negative for p16 loss). By immunohistochemistry, loss of p16 expression was not observed in Spitz nevi (0/24) but was seen in ASTs (7/27; 26%) and spitzoid melanomas (3/19; 16%). By H score, p16 expression was significantly higher in Spitz nevi relative to ASTs or spitzoid melanomas. Similarly, copy number aberrations of CDKN2A by FISH were absent in Spitz nevi but were found in 2 (9.5%) of 21 ASTs and 4 (33%) of 12 spitzoid melanomas. Our findings from this large cohort suggest that p16 aberrations are highly specific for borderline and malignant spitzoid neoplasms relative to Spitz nevi. Similar to ASTs, p16 loss in spitzoid melanomas may occur in the presence or absence of genomic CDKN2A loss.

Original languageEnglish (US)
Pages (from-to)152-160
Number of pages9
JournalHuman pathology
Volume58
DOIs
StatePublished - Dec 1 2016

Funding

The authors thank Nisha Meireles for assistance with retrieval of clinical data from the UMHS Multidisciplinary Melanoma Clinic database. P. W. H. is a recipient of the Dermatopathology Research Career Development Award from the Dermatology Foundation.

Keywords

  • CDKN2A
  • Fluorescence in situ hybridization
  • Immunohistochemistry
  • Melanoma
  • p16
  • Spitz

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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