title: Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions.
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.
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109. Electronic address: paulharm@med.umich.edu.
authors: Paul W
authors: PW
authors: Harms
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: Thomas L
authors: TL
authors: Hocker
authors: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109.
authors: Lili
authors: L
authors: Zhao
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: May P
authors: MP
authors: Chan
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: Aleodor A
authors: AA
authors: Andea
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: Min
authors: M
authors: Wang
authors: Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: Kelly L
authors: KL
authors: Harms
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: Michael L
authors: ML
authors: Wang
authors: Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI 48202.
authors: Shannon
authors: S
authors: Carskadon
authors: Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI 48202.
authors: Nallasivam
authors: N
authors: Palanisamy
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI 48109; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109.
authors: Douglas R
authors: DR
authors: Fullen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000032:analysis / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D018332:Nevus, Epithelioid and Spindle Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18
keywords: CDKN2A; Fluorescence in situ hybridization; Immunohistochemistry; Melanoma; Spitz; p16