Spatial distribution of osteopontin, CD44v6 and podoplanin in the lining epithelium of odontogenic keratocyst, and their biological relevance

- Recent WHO reclassified odontogenic keratocyst (OKC) as an odontogenic jaw cyst.
- Its local invasiveness and recurrence potential remain ill-understood.
- Spatial distribution of pro-invasive factors in OKC lining epithelium was studied.
- OPNlow, CD44v6high and podoplaninhigh are distinct epithelial signatures of OKC.
- No significant correlations between pro-invasive factors and OKC clinical parameters.

Background and aimsThe odontogenic keratocyst (OKC) remains the most challenging jaw cyst to treat because of its locally-aggressive behaviour and high recurrence potential. Emerging evidence suggests that osteopontin, its receptors CD44v6 and integrin αv, and podoplanin, have a role in the local invasiveness of this cyst. However the spatial distribution characteristics of these pro-invasive markers in the lining epithelium of OKC, and their association with the clinicopathologic parameters of OKC are largely unexplored. This study sought to address these issues in comparison with dentigerous cysts (DCs) and radicular cysts (RCs) and to evaluate their biological relevance.MethodsA sample consisting of 20 OKC cases, 10 DCs and 10 RCs was subjected to immunohistochemical staining for osteopontin, CD44v6 and integrin αv, and podoplanin, and semiquantitative analysis was performed.ResultsAll factors (except integrin αv) were detected heterogeneously in the constitutive layers of the lining epithelium in all three cyst types. Key observations were significant upregulation of CD44v6 and podoplanin in OKC compared to DCs and RCs, suggesting that these protein molecules may play crucial roles in promoting local invasiveness in OKC (P < 0.05). Osteopontin underexpression and distribution patterns were indistinctive among all three cysts indicating its limited role as pro-invasive factor. Clinical parameters showed no significant correlations with all protein factors investigated.ConclusionsPresent findings suggest that an osteopontinlow CD44v6high and podoplaninhigh immunoprofile most probably represent epithelial signatures of OKC and are markers of local invasiveness in this cyst.