title: Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.
abstract: Mammalian epidermis, which is composed of hair follicles, sebaceous glands, and interfollicular epidermis, is maintained by discrete stem cells. In vivo lineage tracing demonstrated that murine LGR5 cells are mainly responsible for hair follicle regeneration whereas LGR6 cells generate sebaceous glands and interfollicular epidermis. However, little is known about their expression in the human skin tumors. In this study, we investigated the expression profile of LGR5 and LGR6 in a variety of human skin tumors including basaloid tumors with follicular differentiation (94 basal cell carcinomas, 18 trichoepitheliomas, 3 basaloid follicular hamartomas, and 12 pilomatricomas) and tumors with ductal differentiation (7 eccrine poromas, 8 hidradenomas, and 5 spiradenomas). LGR5 expression was highest in basal cell carcinomas (BCCs) followed by trichoepitheliomas (TEs) and basaloid follicular hamartomas. LGR6 had the same expression pattern as LGR5, even though its expression was lower. Interestingly, LGR6 expression was detected in stromal cells around the tumor and papillary mesenchymal bodies of TEs but not in stromal cells of BCCs, suggesting different characteristics of tumor-associated fibroblasts between TEs and BCCs. It was unexpected to find that pilomatricomas exclusively expressed LGR6, and its expression was limited to the basaloid cells. Notably, LGR6-positive cells were observed in sweat gland ductal cells in normal skin. This might explain, in part, the finding that LGR6 expression was relatively higher in basaloid tumors with ductal differentiation than in those with follicular differentiation. In particular, spiradenomas displayed the same distribution pattern of LGR6 as normal sweat glands, suggesting the possibility of LGR6-positive cells as tumor stem cells. In conclusion, we documented the different expression patterns of stem cell markers, LGR5 and LGR6 in various skin tumors. These data may provide important insights to understand the origin and development of basaloid skin tumors.
authors.affiliation: Department of Pathology, Jeju National University School of Medicine, Jeju, South Korea.
authors.forename: Bo Gun
authors.initials: BG
authors.lastname: Jang
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799, South Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Pathology, Jeju National University School of Medicine, Jeju, South Korea.
authors.forename: Hye Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Plastic Surgery, Jeju National University School of Medicine, Jeju, South Korea.
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Shin
authors.affiliation: Department of Dermatology, Jeju National University School of Medicine, Jeju, South Korea.
authors.forename: Min Seok
authors.initials: MS
authors.lastname: Cheon
authors.affiliation: Department of Dermatology, Jeju National University School of Medicine, Jeju, South Korea.
authors.forename: Jae Wang
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799, South Korea. woohokim@snu.ac.kr.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D006201:Hair Diseases / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013544:Sweat Gland Neoplasms / Q000473:pathology*; D046888:Tissue Array Analysis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C116884:LGR5 protein, human; C417544:LGR6 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Basal cell carcinoma; In situ hybridization; LGR5; LGR6; Stem cell