MATERIALS AND RESULTS: Thirty-five paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1), and primary cultures of ameloblastoma stromal fibroblasts (ASF) were used. Immunohistochemistry, MTT assay, Western blotting, and RT-PCR were performed on these samples. Parenchyma-stromal CCN2 overexpression correlated significantly with fibrous-type stroma, but not with myxoid-type stroma, suggesting a role of CCN2 in fibrosis (P < 0.05). Recombinant CCN2 induction of enhanced ASF proliferation in AM-1 medium supports this view. Conversely, BMP4 and TGF-β were expressed in myxoid-type fibroblasts, but little expression was found in parenchyma. RANKL-positive and CD68-positive stromal cell populations were significantly greater in myxoid-type tumor areas than in fibrous-type tumor areas, while a higher Ki-67 labeling index was recorded in ameloblastoma with fibrous-type stroma. These data suggest that stromal properties influence bone resorption-related activities and growth rates, respectively.
CONCLUSIONS: These results suggest that the effects of secreted growth factors are governed by ameloblastoma parenchyma-stromal interactions. CCN2 promotes fibrogenesis independent of TGF-β signaling. Absence of CCN2 expression is associated with a phenotypic switch to a myxoid-type microenvironment that is conducive for TGF-β/BMP4 signaling to promote osteoclastogenesis.
MATERIALS AND METHODS: Thirty-nine formalin-fixed paraffin-embedded ameloblastoma cases comprising unicystic ameloblastoma (n=19) and solid/multicystic ameloblastoma (n=20) were subjected to IHC staining for IL-1α, IL-1β, IL-6 and IL-8. A semi-quantitative method was used to evaluate the expression levels of these cytokines according to cell types in the tumoural parenchyma and stroma.
RESULTS: Major findings were upregulations of IL-1α and IL-6 in SMA compared to UA. Both cytokines were heterogeneously detected in the tumoural parenchyma and stroma. Within the neoplastic epithelial compartment, IL-1α expression was more frequently detected in PA-like cells in UA whereas it was more frequently encountered in SR-like cells in SMA. IL-6 demonstrated higher expression levels in the stromal compartment of SMA. IL-1β and IL-8 were markedly underexpressed in both tumour subsets.
CONCLUSIONS: Overexpression of IL-1α in SMA suggests that this growth factor might play a role in promoting bone resorption and local invasiveness in this subtype. The expression levels of IL-1α and IL-6 in three cellular localizations indicate that parenchymal-stromal components of ameloblastoma interact reciprocally via IL-1α and IL-6 to create a microenvironment conducive for tumour progression.
OBJECTIVES: To determine the risk of the contralateral mucosa in patients presenting with oral PMDs.
MATERIALS AND METHODS: Sixty individuals with PMDs were selected for this study. These comprised 32 (53.3%) Indians, 23 (38.3%) Chinese, four (6.7%) Malays and one (1.7%) Nepalese. All selected cases had histopathological confirmation of their primary existing lesion as inclusion criteria. Cases that subsequently presented with a lesion in the corresponding anatomical site also underwent scalpel incisional biopsy on this second lesion to verify its diagnosis. The remaining cases that presented with unilateral PMDs at the time of study were subjected to a cytobrush biopsy on the normal looking contralateral mucosa.
RESULTS: A total of 70 primary PMDs were detected in 60 patients. The most common PMD found was oral lichen planus (n=40, 57.1%). Of the 60 patients studied, 28 (46.6%) exhibited bilateral lesions either synchronously (n=21, 35.0%) or metachronously (n=7, 11.6%). The remaining cases that had undergone cytobrush biopsy on the corresponding anatomical site yielded normal cytological results.
CONCLUSIONS: Present findings demonstrated that patients presenting with PMDs in the upper aerodigestive tract are at a greater risk of developing a second lesion most probably in the contralateral anatomical site.