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Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors

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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.

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Authors and Affiliations

  1. Department of Pathology, Jeju National University School of Medicine, Jeju, South Korea

    Bo Gun Jang & Hye Sung Kim

  2. Department of Pathology, Seoul National University College of Medicine, 28 Yeongeon-dong, Seoul, 110-799, South Korea

    Cheol Lee & Woo Ho Kim

  3. Department of Plastic Surgery, Jeju National University School of Medicine, Jeju, South Korea

    Myung Soo Shin

  4. Department of Dermatology, Jeju National University School of Medicine, Jeju, South Korea

    Min Seok Cheon & Jae Wang Kim

Authors
  1. Bo Gun Jang
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  2. Cheol Lee
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  3. Hye Sung Kim
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  4. Myung Soo Shin
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  5. Min Seok Cheon
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  7. Woo Ho Kim
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Corresponding author

Correspondence to Woo Ho Kim.

Ethics declarations

This study was approved by the Institutional Review Board of Jeju National University Hospital and Seoul National University Hospital, respectively.

Funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number HI14C1277).

Conflicts of interest

The authors declare no conflict of interest.

Additional information

Bo Gun Jang and Cheol Lee contributed equally to this work.

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Jang, B.G., Lee, C., Kim, H.S. et al. Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors. Virchows Arch 470, 301–310 (2017). https://doi.org/10.1007/s00428-016-2061-3

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  • DOI: https://doi.org/10.1007/s00428-016-2061-3

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