Prognostic relevance of clinicopathological factors in sporadic and syndromic odontogenic keratocysts: A comparative study.

BACKGROUND: Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs. OBJECTIVES: This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC. MATERIAL AND METHODS: We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence. RESULTS: We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio. CONCLUSIONS: The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.

Immunoexpression of RANK, RANKL and OPG in sporadic odontogenic keratocysts and their potential association with recurrence.

BACKGROUND: Odontogenic keratocysts (OKCs) are clinically aggressive lesions with relatively high recurrence rates. Dysregulation of functional equilibrium in the RANK/RANKL/OPG system is responsible for osteolysis associated with the development of OKCs. Previously published findings imply that immunoexpression of these 3 proteins may correlate with bone resorption activity in OKCs. OBJECTIVES: The rationale behind this study was to assess the potential for receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) expression, as well as RANKL/OPG expression ratio, to serve as prognostic indicators for OKC recurrence. MATERIAL AND METHODS: We investigated the immunoexpression patterns of RANK, RANKL and OPG, and their correlation with recurrence rates, in 41 patients with OKCs treated with enucleation. RESULTS: We found no statistically significant differences between recurrent and non-recurrent cysts in terms of either: epithelial (p = 0.404) and stromal (p = 0.469) immunoreactivity of RANK; epithelial (p = 0.649) and stromal (p = 0.198) immunoreactivity of RANKL; or epithelial (p = 1) and stromal (p = 0.604) immunoreactivity of OPG. We also did not find significant differences in the distribution of cases with respect to ratios of RANKL/OPG immunostaining scores between recurrent and non-recurrent OKCs, both in the epithelium and in the connective tissue (p = 1 and p = 0.237, respectively). CONCLUSIONS: Our results suggest that immunoexpression levels of RANK, RANKL and OPG at the time of pathological diagnosis, as well as the RANKL/OPG ratio, are not useful as prognostic markers for OKC recurrence.

Investigation of clinicopathological parameters and expression of COX-2, bcl-2, PCNA, and p53 in primary and recurrent sporadic odontogenic keratocysts.

OBJECTIVES: Odontogenic keratocyst (OKC) presents considerable variation in aggressiveness and propensity for recurrence, yet hitherto, no explicit clinicopathological features have been determined to clearly demonstrate the potential for relapse. This retrospective study aims to investigate the prognostic relevance of various clinicopathological features as well as immunoexpression of COX-2, bcl-2, PCNA, and p53 in sporadic OKC. MATERIALS AND METHODS: Among 41 patients with OKC treated by enucleation, the frequency of recurrence for various clinicopathological features as well as immunoexpression for COX-2, bcl-2, PCNA, and p53 was evaluated. RESULTS: The mean follow-up was 8.49 years, and recurrences were ascertained in 29.27% of cases. We found significant differences between recurrent and non-recurrent cysts in terms of multilocularity (P = 0.029), cortical perforation (P = 0.001), and lesion size (P < 0.001). Hazard risk for the recurrence was 3.362 (95% CI 1.066-10.598) for multilocular cysts, 7.801 (95% CI 2.1-28.985) for evidence of cortical perforation, and 1.004 (1.002-1.006) for 1 mm2 of lesion size on panoramic radiographs. We also found that immunoexpression of PCNA significantly correlates with the radiographic evidence of cortical perforation (P = 0.048) and that there is significant positive correlation between expression of COX-2 and bcl-2 (P = 0.001) as well as significant negative correlation between immunoexpression of COX-2 and age (P = 0.002). None of the other analyzed factors were associated with the recurrence. CONCLUSIONS: Larger size, multilocularity, and cortical perforation in sporadic OKC may be correlated with the relapse. CLINICAL RELEVANCE: Immunohistochemical analyses of COX-2, bcl-2, PCNA, and p53 lack prognostic utility in sporadic OKC.