PTCH1 mutations in odontogenic keratocysts: are they related to epithelial cell proliferation?

Mutations in PTCH1 gene are responsible for majority of nevoid basal cell carcinoma syndrome (NBCCS) as well as for some related sporadic neoplasms. Odontogenic keratocysts (OKCs) are locally aggressive jaw lesions that may occur in isolation or in association with NBCCS. Mutations of PTCH1 would lead to constitutive activation of Sonic hedgehog (SHH) signaling pathway and result in aberrant cell proliferation. To clarify the role of PTCH1 in OKCs, mutational analysis was undertaken in eight sporadic and four NBCCS-associated OKCs and six PTCH1 mutations were identified in two sporadic and three NBCCS-associated cases. The epithelial cell proliferation as assessed by Ki67 labeling was studied in a total cohort of 62 OKCs (42 sporadic and 20 syndromic cases) with known PTCH1 status. The epithelial Ki67 labeling in OKCs with PTCH1 mutation was significantly higher than that in cases with no PTCH1 mutation. Furthermore, OKCs harboring PTCH1 truncation-causing mutations showed an even greater Ki67 labeling index than those with non-truncation-causing mutations. These results suggest that PTCH1 mutations, particularly those causing protein truncations, are associated with a subgroup of OKCs showing increased proliferative activity and thus may relate to a phenotype of higher recurrent tendency.