Hypermethylation of the CDKN2A gene promoter is a frequent epigenetic change in periocular sebaceous carcinoma and is associated with younger patient age.
Periocular sebaceous carcinoma is an aggressive neoplasm with significant morbidity and mortality. Its pathogenesis is poorly understood. It is only rarely associated with Muir-Torre syndrome. Previous studies from Asian countries, have suggested that human papillomavirus (HPV) infection plays a role in the pathogenesis and overexpression of p16(INK4a), a surrogate marker of HPV infection, have also been reported. However, data from western countries seem contradictory. In order to clarify and explore the molecular and epigenetic basis of HPV, CDKN2A status and role of microsatellite instability in the development of periocular sebaceous carcinoma, 24 cases of periocular sebaceous carcinoma were analyzed for the expression of p16(INK4a) and mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) via immunohistochemistry. Nested polymerase chain reaction (PCR) and genechip HPV typing were used to detect HPV infection and decide its genotype when present. PCR amplification using a consensus primer pair was also performed to detect β-HPV. The methylation status of CDKN2A promoter region was studied by methylation-specific polymerase chain reaction. HPV-positivity was demonstrated in only one of our cases (HPV 16), while another case showed p16(INK4a) overexpression. All cases showed preserved expression of mismatch repair proteins. CDKN2A promoter hypermethylation was noted in nearly half of our cases (11/24) and was associated with younger patient age (P = .013). Our results showed that periocular sebaceous carcinoma is rarely associated with HPV and microsatellite instability. Higher frequency of CDKN2A promoter hypermethylation in younger patients implies a significant epigenetic role in tumor development in this age group.
Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
Jau-Yu
JY
Liau
Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
Shu-Lang
SL
Liao
Department of Pathology, Cheng Hsin General Hospital, Taipei 11220, Taiwan.
Cheng-Hsiang
CH
Hsiao
Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
Ming-Chieh
MC
Lin
Department of Ophthalmology, Taipei Hospital, Department of Health, New Taipei City 24213, Taiwan.
Hsiao-Ching
HC
Chang
Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan. Electronic address: pathologykimo@gmail.com.
Kuan-Ting
KT
Kuo
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005142:Eyelid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D012626:Sebaceous Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
Human papillomavirus; Periocular sebaceous carcinoma; Promoter hypermethylation; p16(INK4a)