PMID- 38134090
OWN - NLM
STAT- MEDLINE
DCOM- 20231225
LR  - 20240129
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 102
IP  - 51
DP  - 2023 Dec 22
TI  - Immunophenotypic p14 and p16 correlations with CDKN2A mutations in primary 
      multiple and familial melanoma: An observational study.
PG  - e36756
LID - 10.1097/MD.0000000000036756 [doi]
LID - e36756
AB  - Melanoma represents an aggressive malignant tumor, encapsulating frequent loss of 
      differentiation markers, with familial melanoma constituting a relatively 
      commonly encountered entity, in direct relationship with cyclin-dependent kinase 
      inhibitor 2A (CDKN2A). The present study aims to identify the association between 
      the immunohistochemical p14-p16 profile, the molecular CDKN2A findings and 
      clinically diagnosed familial or multiple primary melanomas (MPM). We conducted a 
      5-year retrospective cross-sectional study, on patients diagnosed with familial 
      or MPM. P14 and p16 immunohistochemical staining has been applied on the selected 
      surgical specimens simultaneously with the performance of fluorescence in situ 
      hybridization (FISH) CDKN2A testing. 13 out of the 23 included cases displayed 
      p14 and/or p16 immunohistochemical absence and the main positive relationships 
      were encountered between CDKN2A homozygous deletion and p14 +/- p16 negative 
      immunoreactions. Cases with exclusive p16 absent reaction (n = 7) were more 
      frequently associated with the presence of distant metastases (85.71%), while 
      samples with exclusive p14 immunohistochemical loss exhibited more favorable 
      histopathological prognostic markers. The average percentage of p16-stained 
      nuclei in the superficial dermis and the deep dermis were equal (29.54% for 
      each), therefore infirming its potential predictive and/or prognostic utility. 
      The present study is the first of its type to approach the clinical, evolutionary 
      and immunophenotypic correlations between p14-p16 immunohistochemical testing, 
      CDKN2A molecular biology pattern, familial melanoma and spontaneous MPM in a 
      cohort of Romanian patients. This analysis highlighted the value of singular p16 
      immunohistochemical absence as a predictor for aggressive biological behavior and 
      unfavorable prognosis in familial melanoma and/or MPM, in comparison with the 
      exclusive loss of p14, indifferent to the histopathological subtype. The present 
      study emphasizes the utility of immunohistochemistry as a less expensive method 
      of complementing the current testing arsenal and could represent the starting 
      point for the elaboration of tailored diagnostic and therapeutic algorithms, 
      based on the discovered p14-p16-CDKN2A significant correlation.
CI  - Copyright (c) 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
FAU - Bosoteanu, Luana-Andreea
AU  - Bosoteanu LA
AUID- ORCID: 0000-0003-0391-4900
AD  - Department of Dermatovenerology, "Elias" Emergency University Hospital, 
      Bucharest, Romania.
AD  - Institute of Doctoral Studies, Doctoral School of Medicine, "Ovidius" University 
      of Constanta, Constanta, Romania.
FAU - Gheorghe, Emma
AU  - Gheorghe E
AD  - Department of Dermatology, "Sf. Apostol Andrei" Emergency County Hospital, 
      Constanta, Romania.
AD  - Department of Histology, Faculty of Medicine, "Ovidius" University of Constanta, 
      Constanta, Romania.
FAU - Aschie, Mariana
AU  - Aschie M
AD  - Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, 
      Constanta, Romania.
AD  - Department of Pathology, Faculty of Medicine, "Ovidius" University of Constanta, 
      Constanta, Romania.
AD  - Department VIII - Medical Sciences, Academy of Romanian Scientists, Bucharest, 
      Romania.
FAU - Cozaru, Georgeta Camelia
AU  - Cozaru GC
AD  - Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, 
      Constanta, Romania.
AD  - Center for Research and Development of the Morphological and Genetic Studies of 
      Malignant Pathology (CEDMOG), Constanta, Romania.
FAU - Deacu, Mariana
AU  - Deacu M
AD  - Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, 
      Constanta, Romania.
AD  - Department of Pathology, Faculty of Medicine, "Ovidius" University of Constanta, 
      Constanta, Romania.
FAU - Orasanu, Cristian Ionut
AU  - Orasanu CI
AD  - Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, 
      Constanta, Romania.
AD  - Center for Research and Development of the Morphological and Genetic Studies of 
      Malignant Pathology (CEDMOG), Constanta, Romania.
FAU - Bosoteanu, Madalina
AU  - Bosoteanu M
AD  - Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, 
      Constanta, Romania.
AD  - Department of Pathology, Faculty of Medicine, "Ovidius" University of Constanta, 
      Constanta, Romania.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (CDKN2A protein, human)
SB  - IM
MH  - Humans
MH  - *Melanoma/genetics
MH  - Retrospective Studies
MH  - In Situ Hybridization, Fluorescence
MH  - Melanoma, Cutaneous Malignant
MH  - Homozygote
MH  - Cross-Sectional Studies
MH  - Sequence Deletion
MH  - *Skin Neoplasms/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
PMC - PMC10735120
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2023/12/22 19:43
MHDA- 2023/12/25 06:43
PMCR- 2023/12/22
CRDT- 2023/12/22 13:43
PHST- 2023/12/25 06:43 [medline]
PHST- 2023/12/22 19:43 [pubmed]
PHST- 2023/12/22 13:43 [entrez]
PHST- 2023/12/22 00:00 [pmc-release]
AID - 00005792-202312220-00039 [pii]
AID - 10.1097/MD.0000000000036756 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2023 Dec 22;102(51):e36756. doi: 
      10.1097/MD.0000000000036756.