Expression of SHH, PTCH and SMO to the Hedgehog signal in keratocystic odontogenic tumor

DOI
  • Yamada Koji
    Graduate School of Dentistry (First Department of Oral and Maxillofacial Surgery), Osaka Dental University
  • Wato Masahiro
    Department of Oral Pathology, Osaka Dental University
  • Tsuji Kaname
    First Department of Oral and Maxillofacial Surgery, Osaka Dental University
  • Tanaka Akio
    Department of Oral Pathology, Osaka Dental University
  • Morita Shosuke
    First Department of Oral and Maxillofacial Surgery, Osaka Dental University

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The keratocystic odontogenic tumor (KCOT) is a benign odontogenic tumor of the jaw that occurs in association with nevoid basal cell carcinoma syndrome (NBCCS). In 2005, WHO recommended that the term KCOT replace the term odontogenic keratocyst (OKC), because of the aggressive biological behavior of KCOT, and its expression of the Patched 1 (PTCH) gene that is related to KCOT tumorigenesis. We investigated the co-expression of PTCH with that of sonic hedgehog (SHH), for which PTCH is a receptor, and of smoothened (SMO), a molecule downstream of PTCH signaling to determine if this signaling pathway might be intact in KCOT. We used immunohistochemistry, western blotting and RT-PCR analyses to examine the expression of SHH, PTCH and SMO in surgical specimens of 30 cases of KCOT, 8 cases of the orthokeratinized odontogenic cyst (OOC) and 10 cases of the dentigerous cyst (DC). We also did immunohistochemical analyses of two different epithelial layers, the upper spinous layer and the lower basal layer.<br> Immunohistochemical analysis revealed that the spinous layer of 28 cases and the basal layer of 15 cases were positive for SHH, the spinous layer of all cases and the basal layer of 23 cases were positive for PTCH, and the spinous layer of 28 cases and the basal layer of 15 cases were positive for SMO. Western blotting showed that SHH protein expression, with a molecular weight of 17 kDa, was detected in KCOT, OOC and DC ; a PTCH protein, with a molecular weight of 161 kDa, was observed in a specific pattern in KCOT, and an SMO protein, with a molecular weight of 46 kDa, was observed in KCOT. PCR analysis indicated a specific expression pattern of PTCH in KCOT, OOC and DC. Since PTCH, SHH and SMO were expressed in some cases of KCOT, we think that non-mutated molecules in the SHH pathway may be responsible for the development of KCOT, OOC and DC.

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