Immunohistochemical analysis of cell‐cycle‐ and apoptosis‐related factors in lining epithelium of odontogenic keratocysts

Abstract

We examined the immunohistochemical expressions of cell-cycle- and apoptosis-related factors to investigate the possible role of these factors in odontogenic keratocyst (OKC). Expression of cyclin D1 and p16 protein was detected in the basal and parabasal cells in lining epithelium of OKCs and was found more frequently in basal cell nevus syndrome (BCNS)-associated OKCs than in primary or recurrent OKCs. Positivity for p21 protein was detected in basal to superficial cells, whereas that for p27 protein was detected in parabasal to superficial cells in lining epithelium of OKCs. DNA topoisomerase IIalpha reacted with nuclei in basal and parabasal cells of the lining epithelium of OKCs, and positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. Expression of Fas in suprabasal to superficial cells and expression of Fas-L in basal and parabasal cells were detected in lining epithelium of OKCs. Immunoreactivity for caspase-3 was detected in basal to suprabasal or superficial cells in lining epithelium of OKCs. Single stranded (ss)DNA-positive nuclei were detected in superficial cells in lining epithelium of OKCs. Fas was more broadly distributed in BCNS-associated OKCs than in primary OKCs, and ssDNA-positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. These results suggest that BCNS-associated OKCs might be a distinguishable entity from solitary OKCs.

Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts

“…Moreover, the highest epithelial immunoreactivity to MMP-1 in SOKCs (P Ͻ .05) may help to explain the increased aggressiveness of this lesion, when associated with nevoid basal cell carcinoma syndrome, reported in the literature. 8,10,12 The synthesis and secretion of the proenzyme form of MMP-1 by cultured fibroblasts from OKCs 34 and reports implying a role for MMP-1 in tumor progression 16 and local invasiveness of ameloblastomas, 21 as well as in keratinocyte migration, 18 invasion, and metastasis 20 reinforce the importance of this protease in the OKC biology.…”

“…Therefore, the slightly higher percentage of SOKCs showing strong epithelial immunoreactivity to matrilysins corroborates literature reports that suggest increased aggressiveness of the OKCs associated with nevoid basal cell carcinoma syndrome. 8,10,12 Nevertheless, other studies need to be conducted to confirm if the differences in the expression of MMPs-1, Ϫ7, and Ϫ26 between SOKCs and NSOKCs could be related to more aggressive biological behavior. Thus, clinical and radiographical follow-up data are fundamental.…”

“…7 The OKC can occur sporadically or in association with the nevoid basal cell carcinoma syndrome or Gorlin syndrome, where patients present with many abnormalities, especially basal cell carcinomas, multiple OKCs, skeletal changes and dyskeratosis of the palms and soles. 5,6,8 Analysis of the histopathology 8 and results obtained from studies on cell cycle and apoptosis, [9][10][11] oncogenes, tumoral suppressor genes, 11 and extracellular matrix composition 12 support the existence of a distinct biological behavior between OKCs associated with nevoid basal cell carcinoma syndrome (SOKCs) and nonsyndrome OKCs (NSOKCs). In general, SOKCs have higher growth and infiltration capacity 10 and a tendency to develop more recurrences 8 than NSOKCs do.…”

Cell proliferation and apoptosis in ameloblastomas and keratocystic odontogenic tumors

“…Since KOT had been classified as an odontogenic cyst, several authors have compared cell proliferation between KOT and odontogenic cysts (8,12,13). Although several authors have assessed cell proliferation and apoptosis in the odontogenic epithelium in AM and in the epithelial lining in KOT (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), few studies have compared cell proliferation between these tumors (7,8,11) and no previous study has simultaneously evaluated cell proliferation and apoptotic indexes in AM and KOT, comparing both lesions. Therefore, this is the first study assessing comparatively cell proliferation and apoptosis indexes in AM and KOT, although tissue cell population is controlled by a balance among these processes.…”

“…Several studies have evaluated apoptosis and related apoptotic factors in the odontogenic epithelium of AM and epithelial lining of KOT (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Nevertheless, despite the fact that the cell population is controlled by the balance between cell proliferation and apoptosis, no study has evaluated simultaneously apoptotic and proliferation indexes in AMs and KOTs.…”