Ameloblastic neoplasia spectrum: a cross-sectional study of MMPS expression and proliferative activity.

OBJECTIVE: To compare the proliferation and the expression of matrix metalloproteinases (MMPs; MMP-2 and MMP-9) in solid and unicystic ameloblastomas with ameloblastic carcinomas. STUDY DESIGN: Five cases of ameloblastic carcinoma (AC), 18 cases of solid ameloblastoma (SA), and seven of unicystic ameloblastoma (UA) were selected. The immunohistochemical expression of MMPs was assessed by the percentage of positive tumor cells and stained stroma. The mean argyrophilic nucleolar organizer region (AgNOR) and the percentage of cells with more than one AgNOR per nucleus were evaluated. RESULTS: Statistically significant higher mean AgNOR was observed in AC than in SA and UA. MMP-2 was expressed similarly in tumor and stroma among groups. MMP-9 was higher in the stroma of SA than that of UA (P = .0484). CONCLUSIONS: The cell proliferation was related to the greater aggressiveness of AC. High expression of MMP-2 and MMP-9 in all lesions highlighted the importance of these enzymes in the biology of ameloblastic tumors.

Potential relevance of cyclooxygenase-2 expression in keratocystic odontogenic tumours - an immunohistochemical study.

There is increasing evidence that overexpression of cyclooxygenase-2 (COX-2) plays an important role in tumour growth and spread of tumours by interfering with cell proliferation, cellular adhesion, immune surveillance, apoptosis, and angiogenesis. COX-2 levels are increased in various tumours. In this study, the expression of COX-2 in 116 specimens of keratocystic odontogenic tumours (KCOT) has been analyzed. KCOT is a benign neoplasm of odontogenic origin with an occasionally aggressive behavior leading to high recurrence rates. Formalin-fixed, paraffin-embedded blocks were sectioned and used for hematoxylin-eosin (H&E) staining and incubated with an anti-COX-2 monoclonal antibody for immunohistochemical examination. Detection of the COX-2 antibody was performed with the EnVision kit. Cellular staining pattern for COX-2 was cytoplasmatic, and the staining intensities were semi-quantitatively evaluated as follows: negative (-), mild (±) or strong (+). Mild to strong expression of COX-2 was observed in 83 (71.6%) cases; 34 (29.3%) of which were mild positive and 49 (42.2%) were strong positive. COX-2 stain was detected mainly in the epithelial lining. The expression of COX-2 in KCOT and the current knowledge of the role played by COX-2 in tumorigenesis further strengthen the current concept that the KCOT should be regarded as a neoplasm. Furthermore, the multitude of markers known to be overexpressed in KCOTs is suggestive of what could be called a 'network addiction' pattern, rather than a pathological mechanism dependant on a specific activated/suppressed gene, thus explaining its aggressive behavior.

Absence of hotspot mutations in exons 9 and 20 of the PIK3CA gene in human oral squamous cell carcinoma in the Greek population.

OBJECTIVE: Phosphatidylinositol-3 kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes. Recent studies have reported high frequencies of somatic hotspot mutations in the phosphatidylinositol-3 kinase catalytic alpha (PIK3CA) gene, which encodes for one of these kinases, in several human solid tumors, including oral squamous cell carcinoma (OSCC). The aim of this study was to determine the frequency of hotspot mutations in exons 9 and 20 of the PIK3CA gene in OSCC in the Greek population. STUDY DESIGN: Eighty-six formalin-fixed and paraffin-embedded primary tumor specimens were analyzed by direct genomic DNA sequencing. Chi-square was used for statistical analysis. RESULTS: No hotspot mutations were detected in any of the samples. Two intronic polymorphisms IVS8 and IVS9 were detected, mainly in patients with cancer of the buccal mucosa and lower gingival and alveolus respectively. CONCLUSIONS: PIK3CA hotspot mutations are unlikely to play a major role in the pathogenesis of OSCC in the Greek population.

Establishment and characterisation of an osteoblastic clonal cell line from human mandibular osteosarcoma (HMOS-1).

A human mandibular osteosarcoma cell line, HMOS-1, with osteoblastic phenotypes and tumor-genicity was established. The cell line showed high alkaline phosphatase (ALP) activity immediately after seeding, with its peak around the 7th to 10th day of culture (1.44 mumol/min/mg protein). Parathyroid hormone (PTH) enhanced the ALP activity as well as intracellular cAMP production in a concentration-dependent manner. The effects of PTH on both ALP activity and cAMP production were expressed more strongly at the end stage of logarithmic cell growth than at the resting stage. 1,25 (OH)2D3 also stimulated the ALP activity, but its effect was low and was not different in any of the different culture stages. When these cells were transplanted to BALB/C nude mice, similar tumours to the original one, with abundant osteoids were observed. However, th e synthesis of type 1 collagen was not detected in the culture medium. The results indicate that the HMOS-1 cell line expresses an immature pre-osteoblastic phenotype. Because of these characteristics, HMOS-1 cells should be useful, not only in studies on the differentiated phenotypes of human osteoblasts, but also in studies on the diagnosis, treatment and aetiology of human osteosarcoma of the jaw.

Ultrastructural and histochemical studies of granular-cell ameloblastoma.

Four cases of granular-cell ameloblastoma were studied by light and electron microscopy, histochemistry and electron enzyme histochemistry. Microscopically, granular cells commonly occurred in a follicular pattern, but, in one case, they were in a plexiform pattern. The high activity of acid phosphatase and electron microscopic features revealed that the cytoplasmic granularity was ascribed to the high content of lysosomes. It was speculated that granular-cell ameloblastoma occurs due to the altered dysfunction of tumor cells, and the age factor is related to the pathogenesis of this tumor.

[Desmoid fibroma of bone. An histoenzymological and ultrastructural study of the mandible in one case (author's transl)]. / Fibrome desmoïde osseux. Etude histoenzymologique et ultrastructurale d'un cas de siège mandibulaire.

A case of post-traumatic desmoid tumor of the mandible is reported in a 4-year old girl. This tumor was considered typical clinically and by light microscopy. Four years later, the patient was symptomless, without evidence of recurrence. Histoenzymology showed a high level of leucine aminopeptidase activity. On electron microscopy, a part from a few primitive mesenchymal cells, abnormal fibroblasts represented the principal cellular component. These cells showed evidence of intracytoplasmic collagen fibers synthesis and of myoid differentiation (numerous filaments and endocytosis vacuoles). Myofibroblasts, with a microfibrillary network showing areas of dense osmiophilic condensation in the vicinity of cell membrane were also present. This atypical ultrastructural feature suggests, in this case, the non-neoplastic nature of this lesion. It seems to reflect an abnormal reaction to a traumatic aggression, characterized by proliferation of myofibroblasts (which normally disappear in the late stages of healing) and to have, thus, the signification of pathologic scar.

[Odontogenic induction and ameloblastoma. Histoenzymological and ultrastructural studies (author's transl)]. / Induction odontogène et améloblastome. Données histoenzymologiques et ultrastructurales.

The ameloblastoma is usually thought to be devoid of any odontogenic capacity. However, the histological, ultrastructural and histoenzymological study of 5 cases demonstrates the fairly high level of differentiation of some ameloblastic cells in such neoplasms. Furthermore, it suggests very early stage of epithelio-conjunctive interaction. The tumours consist, in addition to stellate, squamous, clear and dark epithelial cells, of densely packed peripheral columnar cells similar to the differentiated ameloblasts of the inner epithelium of enamel organ (median nucleus, well-developed rough-surfaced endoplasmic reticulum, mitochondria and lysosomal-vacuolar system located in the distal end of the cells). Besides, the cytoplasmic membrane shows some pocket-like apical invaginations similar to early Tomes processes. On the other hand, similarly to physiological odontogenesis, an abundant amount of granulo-filamentous material is found along the lateral cellular membranes, and the basement membrane. This substance, sometimes, is intermingled with vertical collagenous fibers. In some areas, it is disrupted and cytoplasmic invaginations of epithelial cells, passing through these gaps, are connected with neighbouring mesenchymatous cells. In other respects, despite the lack of any odontoblastic differentiation, the high level of alkaline phosphatase activity found in these cells by means of histo and cytoenzymological technics, looks like that of odontogenic mesenchymal cells. These findings seem to demonstrate the histogenetic unicity of odontogenic tumours. These neoplasms, like the embryonary dental organ, are provided with two types of cells (epithelial and stromal cells). Thus, they are able to induce odontogenesis. But, in ameloblastoma, this power of induction is restricted to a very early stage of odontogenesis.

[Central giant cell granuloma: histochemical and ultrastructural study on its histogenesis (author's transl)]. / Das zentrale Riesenzellgranulom: Histochemische und ultrastrukturelle Untersuchunger zur Histogenese

Until now numerous studies on central giant cell granuloma of jawbones have not been able to reveal the histogenesis of this tumourlike lesion. The aim of the present investigation in two surgically proven cases was to study this question by means of histochemical and electron-microscopic methods. Rather similar histochemical properties were shown in giant cells and pericytes of capillary sproute penetrating the granuloma. Cell fusion occurred between both cell types as was observed by electron microscopy. The process of cell fusion is defined by characteristic interdigitations of cell membranes. Therefore pericytes are believed to be the stem cells of multinucleated giant cells in giant cell granuloma. The abundance of giant cells usually occurring in the granuloma might be explained by plenty of capillary sprouts made up by clusters of pericytes. The factors inducing the pericytic cell fusion process are still unknown. The question arises whether cytogenesis of giant cells in giant cell granuloma might be similar in other giant cell lesions or even in the development of multinucleated osteoclasts.