Increased Expression of Interleukin-22 and Its Receptor in Early Oral Neoplastic Lesions

Sohichi Aizawa , Division of Oral Surgery, Department of Otolaryngology Head and Neck Surgery, Nihon University School of Medicine, Tokyo, Japan
Naoko Hirohata , Division of Oral Surgery, Department of Otolaryngology Head and Neck Surgery, Nihon University School of Medicine, Tokyo, Japan
Shihoko Komine Aizawa , Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
Masamichi Komiya PhD, Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan
Satoshi Hayakawa , Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
Statement of the problem

Recently the possible roles of interleukin-22 (IL-22) in pathogenesis in various human neoplasms including oral squamous cell carcinoma have been reported. IL-22, a member of the IL-10 family is produced by immune cells such as natural killer (NK) cells, natural killer T (NKT) cells and activated T cells. IL-22 receptor (IL-22R) is expressed in epithelial cells, but is not present in immune cells. IL-22 has important functions in host defense at mucosal surfaces by promoting the production of antimicrobial peptides from epithelial cells. In addition IL-22 mediates keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes. More than 90% of oral cancer is squamous cell carcinoma and considered that derived from epithelial dysplasia. However, the specific role of IL-22 in epithelial dysplasia especially borderline malignant lesion remains unclear. Therefore, in the present study, we investigated the involvement of IL-22/IL-22R in epithelial dysplasia.

Methods

 Tissue samples were obtained by excision and biopsy between 2007 and 2013. Epithelial dysplasia were classified squamous cell hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in-situ in accordance with the classification of WHO. Disease free lesions of the patients as well as control subjects with benign disorders were used. All the tissues were fixed with formalin and embedded in paraffin, then sectioned at 5 μm thickness. The immunohistochemistry staining was performed using anti-IL-22 antibody and anti-IL-22 receptor antibody. After 1 h incubation at room temperature, the specimens were washed with PBS and then incubated with a secondary antibody. After washing, all specimens were color-developed with diaminobenzidine (DAB) solution and counterstained with haematoxylin. Two or more pathologists performed independent inspection and scoring. The ethics committee of institution approved the study protocol. Written informed consent was obtained from the patients before sampling. The clinical information and routine laboratory examinations were also examined with pathological findings.

Results

The expression of IL-22 was increased in severe dysplasia and carcinoma in-situ compared to the control. In addition IL-22R expressions were also up regulated in epithelial cells of severe dysplasia and carcinoma in-situ cases. On the other hand, in epithelial dysplasia, squamous cell hyperplasia, mild dysplasia, and moderate dysplasia, the IL-22 and IL-22R expressions were not different from control samples.

Conclusions

In the present study, we indicated that the IL-22 and IL-22R expression were increased in high-grade dysplasia tissue. Our results suggest possible importance of IL-22/IL-22R paracrine control in early carcinogenesis in oral cavity.    

Reference

  1. Naher L, Kiyoshima T, Kobayashi I, Wada H, Nagata K, Fujiwara H, Ookuma YF, Ozeki S, Nakamura S, Sakai H: STAT3 signal transduction through interleukin-22 in oral squamous cellcarcinoma. Int J Oncol. 2012 Nov;41(5):1577-86.
  2. Fujita H.: The role of IL-22 and Th22 cells in human skin diseases. J Dermatol Sci. 2013 Oct;72(1):3-8.
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