PMID- 29489509
OWN - NLM
STAT- MEDLINE
DCOM- 20200505
LR  - 20210208
IS  - 1533-4058 (Electronic)
IS  - 1533-4058 (Linking)
VI  - 27
IP  - 6
DP  - 2019 Jul
TI  - The Amount of Melanin Influences p16 Loss in Spitzoid Melanocytic Lesions: 
      Correlation With CDKN2A Status by FISH and MLPA.
PG  - 423-429
LID - 10.1097/PAI.0000000000000633 [doi]
AB  - AIMS: The risk assessment of spitzoid lesions is one of the most difficult 
      challenges in dermatopathology practice. In this regard, the loss of p16 
      expression and the homozygous deletion of CDKN2A, have been pointed in the 
      literature as reliable indicators of high risk. However, these findings are 
      poorly reproducible, and the molecular bases underlying the loss of p16 
      expression remain unclear. We aimed to identify the underlying events causing 
      loss of CDKN2A/p16 in spitzoid tumors. MATERIALS AND METHODS: We evaluated the 
      immunohistochemical expression of p16, and the presence of CDKN2A genetic 
      alterations detected through fluorescence in situ hybridization (FISH) and 
      multiplex ligation-dependent probe amplification (MLPA), in a series of 130 Spitz 
      nevi, 20 atypical spitzoid tumors, and 11 spitzoid melanoma. RESULTS: We found a 
      significant loss of p16 expression in cases with high amount of melanin content 
      in the 3 groups (P<0.000001) and a similar proportion of p16-negative cases in 
      the group of Spitz nevi and atypical spitzoid tumors. MLPA allowed the 
      recognition of CDKN2A microdeletions, which correlated with p16 loss (P=0.01). 
      MLPA and FISH were more accurate than immunohistochemistry to detect CDKN2A 
      alterations; although contrary to MLPA, FISH fails to recognize CDKN2A 
      microdeletions. CONCLUSIONS: According to our results, p16 expression may be 
      useful in the study of cases with atypical features and low melanin content, but 
      it has no value in highly pigmented spitzoid lesions.
FAU - Martinez Ciarpaglini, Carolina
AU  - Martinez Ciarpaglini C
AD  - Biomedical Research Institute INCLIVA.
FAU - Gonzalez, Jose
AU  - Gonzalez J
AD  - Biomedical Research Institute INCLIVA.
FAU - Sanchez, Beatriz
AU  - Sanchez B
AD  - Biomedical Research Institute INCLIVA.
FAU - Agusti, Jaime
AU  - Agusti J
AD  - Department of Pathology, Consorcio Hospitalario Provincial de Castellon.
FAU - Navarro, Lara
AU  - Navarro L
AD  - Biomedical Research Institute INCLIVA.
FAU - Nieto, Gema
AU  - Nieto G
AD  - University of Valencia,Valencia, Spain.
FAU - Monteagudo, Carlos
AU  - Monteagudo C
AD  - Biomedical Research Institute INCLIVA.
AD  - University of Valencia,Valencia, Spain.
AD  - Department of Pathology, Hospital Clinico Universitario de Valencia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Appl Immunohistochem Mol Morphol
JT  - Applied immunohistochemistry & molecular morphology : AIMM
JID - 100888796
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Melanins)
SB  - IM
MH  - Adult
MH  - Biomarkers, Tumor/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Melanins/genetics/*metabolism
MH  - Melanocytes/*physiology
MH  - Melanoma/diagnosis/*metabolism
MH  - Multiplex Polymerase Chain Reaction
MH  - Mutation/genetics
MH  - Nevus, Epithelioid and Spindle Cell/diagnosis/*metabolism
MH  - Skin Neoplasms/diagnosis/*metabolism
MH  - Young Adult
EDAT- 2018/03/01 06:00
MHDA- 2020/05/06 06:00
CRDT- 2018/03/01 06:00
PHST- 2018/03/01 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2018/03/01 06:00 [entrez]
AID - 10.1097/PAI.0000000000000633 [doi]
PST - ppublish
SO  - Appl Immunohistochem Mol Morphol. 2019 Jul;27(6):423-429. doi: 
      10.1097/PAI.0000000000000633.