Epigenetic alterations in metastatic cutaneous carcinoma.
BACKGROUND
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the 2 most common cutaneous carcinomas. Molecular profiles predicting metastasis of these cancers have not been identified.


METHODS
Epigenetic profiles of 37 primary cases of cutaneous SCC and BCC were quantified via the Illumina Goldengate Cancer Panel. Differential protein expression by metastatic potential was analyzed in 110 total cases by immunohistochemical (IHC) staining.


RESULTS
Unsupervised hierarchical clustering analysis revealed that metastatic BCCs had a methylation profile resembling cutaneous SCCs. Metastatic cutaneous SCCs were found to be hypermethylated at FRZB (median methylation: 46.7% vs 4.7%; p = 4 × 10(-5) ). Metastatic BCCs were found to be hypomethylated at MYCL2 (median methylation: 3.8% vs 83.4%; p = 1.9 × 10(-6) ). Immunohistochemical staining revealed few differences between metastatic and nonmetastatic cancers.


CONCLUSIONS
Metastatic primary BCCs and cutaneous SCCs had distinct epigenetic profiles when compared to their nonmetastatic counterparts. Epigenetic profiling may prove useful in future diagnosis and prevention of advanced nonmelanoma skin cancers.
Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.
Owen A
OA
Darr
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan.
Justin A
JA
Colacino
Department of Otolaryngology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Alice L
AL
Tang
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.
Jonathan B
JB
McHugh
Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
Emily L
EL
Bellile
Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.
Carol R
CR
Bradford
Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.
Mark P
MP
Prince
Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.
Douglas B
DB
Chepeha
Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan.
Laura S
LS
Rozek
Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan.
Jeffrey S
JS
Moyer
D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D046888:Tissue Array Analysis
DNA methylation; basal; cutaneous carcinoma; epigenetic; metastasis; squamous