PMID- 26462027
OWN - NLM
STAT- MEDLINE
DCOM- 20160920
LR  - 20231213
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 35
DP  - 2015 Nov 10
TI  - Loss of the epigenetic mark, 5-Hydroxymethylcytosine, correlates with small 
      cell/nevoid subpopulations and assists in microstaging of human melanoma.
PG  - 37995-8004
LID - 10.18632/oncotarget.6062 [doi]
AB  - Melanomas in the vertical growth phase (VGP) not infrequently demonstrate 
      cellular heterogeneity. One commonly encountered subpopulation displays small 
      cell/nevoid morphology. Although its significance remains unknown, such 
      subpopulations may pose diagnostic issues when faced with differentiating such 
      changes from associated nevus or mistaking such regions for nevic maturation 
      (pseudomaturation). That 'loss' of the epigenetic biomarker, 
      5-hydroxymethylcytosine (5-hmC), is a hallmark for melanoma and correlates with 
      virulence prompted us to explore the diagnostic utility and biological 
      implications of 5-hmC immunohistochemistry (IHC) in melanomas with small 
      cell/nevoid subpopulations. Fifty-two cases were included in this study, 
      including melanomas with small cell/nevoid subpopulations (MSCN) or melanomas 
      with pre-existing nevus (MPEN). Semiquantitative and computer-validated 
      immunohistochemical analyses revealed invariable, uniform loss of 5-hmC in the 
      conventional melanoma component. By contrast, the nevic components in MPEN cases 
      demonstrated strong nuclear immunopositivity. In MSCN cases, there was partial to 
      complete loss of 5-hmC restricted to these nevoid areas. Based on recent data 
      supporting tight correlation between 5-hmC loss and malignancy, our findings 
      indicate a potential 'intermediate' biological nature for small cell/nevoid 
      subpopulations. Because 5-hmC assisted in differentiating such regions from 
      associated nevus, the use of 5-hmC as an adjunct to microstaging in difficult 
      cases showing VGP heterogeneity should be further explored.
FAU - Lee, Jonathan J
AU  - Lee JJ
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Cook, Martin
AU  - Cook M
AD  - Department of Histopathology, Royal Surrey County Hospital, Guildford, United 
      Kingdom.
AD  - Cancer Research UK, Manchester Institute, Manchester, United Kingdom.
FAU - Mihm, Martin C
AU  - Mihm MC
AD  - Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Xu, Shuyun
AU  - Xu S
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Zhan, Qian
AU  - Zhan Q
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Wang, Thomas J
AU  - Wang TJ
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Murphy, George F
AU  - Murphy GF
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Lian, Christine G
AU  - Lian CG
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA.
LA  - eng
GR  - P50 CA093683/CA/NCI NIH HHS/United States
GR  - 5P40CA093683-09/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Biomarkers, Tumor)
RN  - 1123-95-1 (5-hydroxymethylcytosine)
RN  - 6R795CQT4H (5-Methylcytosine)
RN  - 8J337D1HZY (Cytosine)
SB  - IM
MH  - 5-Methylcytosine/analogs & derivatives
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/metabolism
MH  - Carcinoma, Small Cell/genetics/metabolism/*pathology
MH  - Cytosine/*analogs & derivatives/metabolism
MH  - *Epigenomics
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Melanoma/genetics/metabolism/*pathology
MH  - Middle Aged
MH  - Neoplasm Staging/*standards
MH  - Nevus, Pigmented/genetics/*pathology
MH  - Prognosis
MH  - Skin Neoplasms/genetics/metabolism/*pathology
MH  - Young Adult
MH  - Melanoma, Cutaneous Malignant
PMC - PMC4741979
OTO - NOTNLM
OT  - 5-hydroxymethylcytosine (5-hmC)
OT  - maturation
OT  - melanoma
OT  - pre-existing nevus
OT  - small cell/nevoid subpopulation
COIS- CONFLICTS OF INTEREST The authors of this manuscript have no conflicts of 
      interest to disclose.
EDAT- 2015/10/16 06:00
MHDA- 2016/09/22 06:00
PMCR- 2015/11/10
CRDT- 2015/10/14 06:00
PHST- 2015/08/05 00:00 [received]
PHST- 2015/09/24 00:00 [accepted]
PHST- 2015/10/14 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2016/09/22 06:00 [medline]
PHST- 2015/11/10 00:00 [pmc-release]
AID - 6062 [pii]
AID - 10.18632/oncotarget.6062 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Nov 10;6(35):37995-8004. doi: 10.18632/oncotarget.6062.