PMID- 27569296
OWN - NLM
STAT- MEDLINE
DCOM- 20170828
LR  - 20191210
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 58
DP  - 2016 Dec
TI  - Loss of p16 expression and copy number changes of CDKN2A in a spectrum of 
      spitzoid melanocytic lesions.
PG  - 152-160
LID - S0046-8177(16)30194-0 [pii]
LID - 10.1016/j.humpath.2016.07.029 [doi]
AB  - 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.
CI  - Copyright A(c) 2016 Elsevier Inc. All rights reserved.
FAU - Harms, Paul W
AU  - Harms PW
AD  - 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.
FAU - Hocker, Thomas L
AU  - Hocker TL
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 
      48109.
FAU - Zhao, Lili
AU  - Zhao L
AD  - Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109.
FAU - Chan, May P
AU  - Chan MP
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 
      48109; Department of Dermatology, University of Michigan Health System, Ann 
      Arbor, MI 48109.
FAU - Andea, Aleodor A
AU  - Andea AA
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 
      48109; Department of Dermatology, University of Michigan Health System, Ann 
      Arbor, MI 48109.
FAU - Wang, Min
AU  - Wang M
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 
      48109.
FAU - Harms, Kelly L
AU  - Harms KL
AD  - Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 
      48109.
FAU - Wang, Michael L
AU  - Wang ML
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 
      48109.
FAU - Carskadon, Shannon
AU  - Carskadon S
AD  - Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, 
      Detroit, MI 48202.
FAU - Palanisamy, Nallasivam
AU  - Palanisamy N
AD  - Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, 
      Detroit, MI 48202.
FAU - Fullen, Douglas R
AU  - Fullen DR
AD  - Department of Pathology, University of Michigan Health System, Ann Arbor, MI 
      48109; Department of Dermatology, University of Michigan Health System, Ann 
      Arbor, MI 48109.
LA  - eng
PT  - Journal Article
DEP - 20160826
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Cyclin-Dependent Kinase Inhibitor p16
MH  - Cyclin-Dependent Kinase Inhibitor p18/analysis/*genetics
MH  - *DNA Copy Number Variations
MH  - Female
MH  - *Gene Dosage
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Melanoma/*enzymology/*genetics/pathology
MH  - Middle Aged
MH  - Nevus, Epithelioid and Spindle Cell/*enzymology/*genetics/pathology
MH  - Predictive Value of Tests
MH  - Reproducibility of Results
MH  - Retrospective Studies
MH  - Skin Neoplasms/*enzymology/*genetics/pathology
MH  - Young Adult
OTO - NOTNLM
OT  - CDKN2A
OT  - Fluorescence in situ hybridization
OT  - Immunohistochemistry
OT  - Melanoma
OT  - Spitz
OT  - p16
EDAT- 2016/08/30 06:00
MHDA- 2017/08/29 06:00
CRDT- 2016/08/30 06:00
PHST- 2016/06/08 00:00 [received]
PHST- 2016/07/20 00:00 [revised]
PHST- 2016/07/28 00:00 [accepted]
PHST- 2016/08/30 06:00 [pubmed]
PHST- 2017/08/29 06:00 [medline]
PHST- 2016/08/30 06:00 [entrez]
AID - S0046-8177(16)30194-0 [pii]
AID - 10.1016/j.humpath.2016.07.029 [doi]
PST - ppublish
SO  - Hum Pathol. 2016 Dec;58:152-160. doi: 10.1016/j.humpath.2016.07.029. Epub 2016 
      Aug 26.