title: Comparison of HER2 gene amplification and KRAS alteration in eyelid sebaceous carcinomas with that in other eyelid tumors.
abstract: Eyelid sebaceous carcinoma (SC) represents a highly aggressive malignancy. Despite the poor prognosis, genetic alterations as potential molecular targets are not available. KRAS mutation and HER2 gene amplification may be candidates related to their genetic alterations. We examined the HER2 and KRAS alteration status in eyelid SCs and compared it with that in other eyelid tumors. The controversial topics of the human papillomavirus (HPV) and p16 expression were also investigated. HER2 amplification was determined by silver in situ hybridization, while immunohistochemistry was performed to study protein expressions in 14 SCs and controls, including 23 other eyelid malignancies and 14 benign tumors. Peptide nucleic acid-mediated PCR clamping and direct sequencing were used to detect KRAS mutations. HER2 protein overexpression was observed in 85.7% (12/14) of the SCs, of which two-thirds showed HER2 gene amplification. HER2 protein overexpression and HER2 amplification were found more frequently in eyelid SCs than in other eyelid tumors. All SCs harbored wild type KRAS genes. No HPV infections were identified in the SCs. Nevertheless, p16 overexpression was found in 71.4% (10/14) of SCs, irrespective of the status of HPV infection. Furthermore, p16 overexpression in eyelid SCs was also significantly higher than that in other eyelid tumors. HER2 protein overexpression, HER2 gene amplifications, and wild type KRAS genes are common in eyelid SCs. HER2 gene amplification may represent potential therapeutic targets for the treatment of eyelid SCs.
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 431-070, Gyeonggi-do, Republic of Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 445, Gil 1-dong, Gangdong-gu, Seoul 134-701, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 445, Gil 1-dong, Gangdong-gu, Seoul 134-701, Republic of Korea.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 445, Gil 1-dong, Gangdong-gu, Seoul 134-701, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Ophthalmology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 431-070, Gyeonggi-do, Republic of Korea.
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 445, Gil 1-dong, Gangdong-gu, Seoul 134-701, Republic of Korea. Electronic address: slee@hallym.or.kr.
authors.forename: Samuel
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 431-070, Gyeonggi-do, Republic of Korea. Electronic address: hyerim@hallym.or.kr.
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Park
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics*; D005142:Eyelid Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012626:Sebaceous Gland Neoplasms / Q000235:genetics*
keywords: Amplification; Eyelid; HER2; KRAS; Sebaceous carcinoma