Expression of Matrix Metalloproteinases 7 and 9, Desmin, Alpha-Smooth Muscle Actin and Caldesmon, in Odontogenic Keratocyst Associated with NBCCS, Recurrent and Sporadic Keratocysts.

Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior.

Expression of Beta-Catenin, Cadherins and P-Runx2 in Fibro-Osseous Lesions of the Jaw: Tissue Microarray Study.

Fibrous dysplasia (FD) and hyperparathyroidism-jaw tumor syndrome (HPT-JT) are well-characterized benign bone fibro-osseous lesions. The intracellular mechanism leading to excessive deposition of fibrous tissue and alteration of differentiation processes leading to osteomalacia have not yet been fully clarified. Tissue Microarray (TMA)-based immunohistochemical expression of ß-catenin, CK-AE1/AE3, Ki-67, cadherins and P-Runx2 were analyzed in archival samples from nine patients affected by FD and HPT-JT and in seven controls, with the aim of elucidating the contribution of these molecules (ß-catenin, cadherins and P-Runx2) in the osteoblast differentiation pathway. ß-catenin was strongly upregulated in FD, showing a hyper-cellulated pattern, while it was faintly expressed in bone tumors associated with HPT-JT. Furthermore, the loss of expression of OB-cadherin in osteoblast lineage in FD was accompanied by N-cadherin and P-cadherin upregulation (p < 0.05), while E-cadherin showed a minor role in these pathological processes. P-Runx2 showed over-expression in six out of eight cases of FD and stained moderately positive in the rimming lining osteoblasts in HPT-JT syndrome. ß-catenin plays a central role in fibrous tissue proliferation and accompanies the lack of differentiation of osteoblast precursors in mature osteoblasts in FD. The study showed that the combined evaluation of the histological characteristics and the histochemical and immunohistochemical profile of key molecules involved in osteoblast differentiation are useful in the diagnosis, classification and therapeutic management of fibrous-osseous lesions.

Central odontogenic fibroma of the mandible: A case report with diagnostic considerations.

INTRODUCTION: Odontogenic fibroma (OF), a rare odontogenic tumor of mesodermal origin, has been thought to originate from either dental follicle, periodontal ligament, or dental papilla [1]. Different studies reported high variability in the incidence rate as being between 3 and 23% of all odontogenic tumors [2,3]. OF manifests a dual character at the histopathological examination showing odontogenic epithelial structures mimicking those observed in biopsy of ameloblastoma and, in addition, peculiar fragments of cellular stroma. The clinical and radiological features of OF are similar to other odontogenic and/or non-odontogenic tumours and the differential diagnosis may first occur at fine-needle aspiration biopsy. PRESENTATION OF CASE: In the case reported, a young patient showed a localized gingival enlargement involving radiologically the superior margin of the right angle of the mandible and associated with an un-erupted tooth. The morphological characteristics together with clinical and radiologic findings confirmed the tumor to be a central odontogenic fibroma (COF) with secondary gingival involvement. DISCUSSION AND CONCLUSION: Benign odontogenic tumors may be distinguished from other odontogenic/non-odontogenic neoplasias and from malignant tumours through a cytologic differential diagnosis as treatment differs accordingly.

Clinical significance of kallikrein-related peptidase-4 in oral cancer.

Kallikrein-related-peptidase-4 (KLK4), a serine protease originally discovered in developing tooth with broad target sequence specificity, serves vital functions in dental enamel formation. KLK4 is involved in degradation of extracellular matrix proteins and it is thought that this proteolytic activity could also promote tumor invasion and metastasis. Recent studies have associated KLK4 expression with tumor progression and clinical outcome, particularly in prostate and ovarian cancer. Very little is known in regard KLK4 involvement in oral squamous cell carcinomas (OSCCs). Our objective was to investigate KLK4 expression in OSCC pathogenesis and disease progression. KLK4 expression was evaluated by immunohistochemistry, western blots and zymograms in OSCC lines. Invasion assays using high versus low/undetectable KLK4-expressing OSCC cell lines were performed jointly with KLK4 siRNA inhibition. A large collection of OSCC specimens was evaluated for KLK4 expression and correlation with patients' characteristics and outcomes were determined. Our data indicate that KLK4 is differentially expressed in oral carcinomas. OSCC cell lines with high invasive and metastatic potential have the highest levels of KLK4 expression. KLK4 mRNA and protein expression correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines. Consistently, KLK4 expression is stronger in primary tumors that later either recurred or developed metastases, suggesting that its preferential expression in OSCC might contribute to individual tumor biology. Therefore, this study provides supportive evidence in favor of a prognostic value for KLK4 in OSCC and suggests that KLK4 could serve as a potential therapeutic target in patients with oral cancer.

Volumetric changes after sinus augmentation using blocks of autogenous iliac bone or freeze-dried allogeneic bone. A non-randomized study.

OBJECTIVES: To compare volumetric bone changes after sinus augmentation for implant positioning using blocks of autogenous iliac bone or freeze-dried allogeneic bone (FDBA) from the hip. Variables were compared between the two sources and for each surgical procedure at set times (pre- and post-augmentation procedure). PATIENTS AND METHODS: A non-randomized retrospective chart review of 7 patients who had autogenous and 7 allogeneic block grafts was carried out (1 procedure per patient). Analysis of Computer Tomographic (CT) data of maxillary sinuses, acquired with high-speed, double-detector CT scanner, was performed using dentascan software. The change between the preoperative (T0) and postoperative volume was measured at 4-6 months (T2) and 1.5 year after transplantation (T3). Annual- and overall-rates of bone change were calculated for the two sources. RESULTS: All patients were partially edentulous with a residual maxillary floor thickness in the planned implant insertion sites of 2.7 (0.5) mm and 2.8 (0.5) mm for allogeneic and autogenous procedures respectively. From identical intraoperative volume of grafts (2.25 cc at T1), volumetric changes were recorded at T2 and T3. The final volume of the grafts was 1.44 cc for allogeneic group and 1.78 cc for the autogenous group. Significant volumetric changes over time of transplanted grafts for both sources (23% for autograft and 18% for allograft) were found at T2. At 1.5-years post-operatively comparisons of volumes and rates of bone loss between sources were not statistically significant. No failure was recorded for either bone grafts or dental implants. CONCLUSIONS: Short-term sinus grafting procedure for dental implant placement performed with FDBA showed an outcome close to that reported for autogenous bone. Volumetric changes were comparable between the sources. These data suggest that performing maxillary sinus augmentation with dry-preserved bone allogeneic materials in block form could be considered even when the residual floor thickness is less than 3 mm.

Expression analysis of SPARC/osteonectin in oral squamous cell carcinoma patients: from saliva to surgical specimen.

Oral squamous cell carcinoma (OSCC) remains a significant cause of morbidity and mortality, with approximately 540,000 new cases annually worldwide. The molecular mechanisms related to the pathogenesis of this disease are still poorly understood. The discovery of a molecular marker that allows the early detection of this cancer, which can be easily identified in biological samples, such as saliva, without intervening in advanced stages, is a challenge. Numerous studies have identified a panel of molecular markers differently expressed in OSCC and normal oral mucosa. In particular, it was found an aberrant expression of matricellular glycoprotein SPARC. SPARC is involved in normal tissue remodeling, regulating the deposition of extracellular matrix, but also in neoplastic transformation. In fact, aberrant SPARC expression was detected both in stromal cells associated with cancer and in tumor cells. The aim of our study was the evaluation of SPARC on a retrospective series of 119 OSCC cases and the validation of the obtained data on a prospective series of 27 patients with OSCC, of whom we have previously collected saliva, and smeared material. The obtained results were correlated with each other and with clinical pathological parameters at our disposal. The study demonstrated a prognostic value of SPARC, especially with regard to its expression in the stroma surrounding OSCC (P < 0.05).

Expression of beta-catenin in human tooth germ.

OBJECTIVE: To evaluate beta-catenin expression in human tooth germ development. STUDY DESIGN: Specimens of 7 human fetuses aged between the ninth and sixteenth week were examined for beta-catenin expression by immunohistochemistry. RESULTS: In the bud stage, we observed catenin membranous positivity for all primitive dental lamina and dental ridge cells, cytoplasmic positivity for tooth bud and intense nuclear positivity for early-condensed dental mesenchyme. The cap stage was marked by intense cytoplasmic and nuclear positivity in the outer and inner enamel epithelium and the dental papilla and by moderate cytoplasmic positivity in the enamel knot. In the early bell stage, we noted strong cytoplasmic and nuclear staining in the inner and outer enamel epithelium, only moderate membranous and cytoplasmic staining in the stellate reticulum, a high percentage of intense nuclear positivity in the dental papilla and strong focal nuclear and cytoplasmic positivity in the dental sac. CONCLUSION: All areas with close contact between epithelial structures and ectomesenchymal cells showed increased expression of delocalized cytoplasmic and nuclear beta-catenin. Nuclear localization, tissue expression pattern and timing suggest a pivotal role for beta-catenin in the transcriptional activation of genes probably involved in the mesenchyme-epithelial interactions on which human tooth development is based.