Immunohistochemical expression of vascular endothelial growth factor (VEGF) in different types of odontogenic cysts.

The objective of the present study was to evaluate vascular endothelial growth factor (VEGF) expression in different types of odontogenic cysts. A total of 25 parakeratotic odontogenic keratocysts (POKCs), 16 orthokeratotic odontogenic keratocysts (OOKCs), and 28 follicular cysts (FCs) were evaluated semiquantitatively for immunohistochemical analysis of VEGF in epithelial cells, endothelial cells of blood vessels, inflammatory cells and focally stromal cells. A significant different expression of VEGF in all cell components was found in keratocysts compared to FCs. The POKCs (80%) and OOKCs (68%) showed more than 50% VEGF positive epithelial cells, whereas the majority of FCs (71%) were either negative in the epithelium or showed less than 10% positive cells. Similarly, the POKCs (88%) and OOKCs (68%) showed more than 50% positive endothelial cells, whereas the FCs (75%) were either negative or showed less than 10% VEGF positive endothelial cells. The highest percentage of cases with score 2 positivity in the stromal cells was observed in POKCs (68%); OOKCs showed a score 2 positivity in 44%, score 1 in 31% and score 0 in 25%, whereas 68% of FCs showed a score 0, 25% a score 1 and only 7% of cases showed a score 2. No statistically significant differences were observed between POKCs and OOKCs in VEGF expression in the epithelial and endothelial cells, whereas the positivity score in stromal cells was significantly higher in POKCs compared to OOKCs. The present results can support the hypothesis that angiogenesis is an active mechanism in the invasive growth of the OKC.

CD10 expression in stromal cells of ameloblastoma variants.

OBJECTIVE: We performed an immunohistochemical study in a series of ameloblastomas with different histology to explore the existence of a correlation between CD10 immunoreactivity in peritumoral stromal cells and the type of ameloblastoma with a high risk of local recurrence. STUDY DESIGN: A total of 45 ameloblastomas (18 unicystic [UA], 4 peripheral [PA], 23 solid/multicystic [SA]) were evaluated. Cases showing immunoreactivity for CD10 in < and > or =10% of stromal cells around tumoral epithelial islands, were considered, respectively, negative and positive. Correlations between stromal CD10 expression and histopathologic types with low and high risk of recurrence were evaluated by statistical analysis. RESULTS: SA cases showed a significantly higher percentage of stromal CD10-positive cells than the UA and PA variants. A strong intensity of immunostaining was observed only in SA. CONCLUSIONS: Our results suggest that CD10 expression might be associated with stromal invasion in ameloblastoma variants with a high risk of recurrences.

Peripheral dentinogenic ghost cell tumor of the gingiva.

BACKGROUND: A dentinogenic ghost cell tumor is a locally invasive neoplasm that is characterized by ameloblastoma-like islands of epithelial cells in a mature connective tissue stroma. METHODS: A 43-year-old male patient presented a well-circumscribed sessile, exophytic mass of the gingiva with a diameter of 2 cm located in the canine area of the right maxilla. The lesion was enucleated. RESULTS: The lesion showed odontogenic epithelium, ghost cells, dentinoid material, and giant cells. The final microscopic diagnosis was a dentinogenic ghost cell tumor. CONCLUSIONS: A dentinogenic ghost cell tumor is an extremely rare tumor, and only a few cases have been reported in the English literature. The peripheral, extraosseous lesion can be easily confused with other gingival lesions such as reactive or inflammatory lesions or other peripheral odontogenic tumors. The clinical appearance of all of these lesions is similar; therefore, the definitive diagnosis depends on histology, and a biopsy with a microscopic examination is mandatory.

Oral lichen planus treated with 13-cis-retinoic acid (isotretinoin): effects on the apoptotic process.

The aim of the present study is to verify the efficacy of isotretinoin in oral lichen planus (OLP). In a double-blind study, ten patients with biopsy-proven OLP were treated for 4 months with 0.1% isotretinoin gel and another ten patients with placebo. At the end of the first period of observation, the patients who had been given the placebo were given isotretinoin for a further 4 months. A complete response was defined as the disappearance of the lesions as assessed by inspection, whereas a partial response was defined as a 50% or more reduction in the size of the lesions. All patients treated with isotretinoin showed a significant improvement of the oral lesions, whereas in the patients who were given the placebo, the size of the lesions remained the same. The patients who were given isotretinoin after the placebo showed a reduction in lesions. In total, there were ten complete and ten partial responses. Lesions were analysed histologically and immunohistochemically with antibodies against bcl-2 and Ki-67. Ki-67 and bcl-2 have statistical significant increased values from before to after treatment, whereas apoptotic bodies decreased one. All these facts could have contributed to the partial or complete regression of OLP lesions. The increase in Ki-67 positive cells show that the epithelium requires for enhanced proliferation and healing. The present results revealed a disturbed cell death programme in OLP that could underline an abnormal epithelial differentiation. The results of this pilot study show that the topical use of isotretinoin is effective in treating OLP.

KAI-1 protein expression in odontogenic cysts.

The KAI-1 tumor suppressor gene is widely distributed in normal tissues and its down-regulation may be correlated with the invasive phenotype and metastases in several different epithelial tumors. The aim of the present study was an evaluation of KAI-1 expression in radicular cysts (RC), follicular cysts (FC), orthokeratinized keratocysts (OOKC), and parakeratinized keratocysts (POKC). Eighty-five odontogenic cysts, 28 RC, 22 FC, and 35 OKC (16 OOKC, 19 POKC) were selected. All the POKC were negative and only four of 16 of the OOKC were positive for KAI-1. On the contrary, all RC and FC cases were positive and immunoreactivity for KAI-1 was detected throughout all the layers of the cyst epithelium. The lack of KAI-1 expression in POKC could help to explain the differences in the clinical and pathologic behavior of OKC and, according to what has been reported for epithelial tumors, could be related to the increased aggressive behavior and invasiveness of OKC.

Soft tissue myxoma: report of an unusual case located on the gingiva.

BACKGROUND: Soft tissue myxoma of the oral cavity is rare. Only three cases of myxoma of gingiva have been reported in the literature. We present a case of soft tissue myxoma arising from the left maxillary adherent gingiva in a 42-year-old male [correction of female] patient. METHODS: Histological examination showed spindle-shaped cells in a myxoid stroma. Immunohistochemical stains with S-100 protein were negative, while those with vimentin were positive. RESULTS: Clinical examination revealed a soft tissue mass, with tense elastic consistency on palpation. The overlying mucosa was normal and healthy. A clinical diagnosis of fibroma was given. Histological examination showed spindle-shaped and stellate cells, arranged in a myxoid fibrous stroma, with collagen fibres distributed uniformly. Scattered islands or strands of inactive odontogenic epithelium were present. On the basis of the histological and immunohistochemical findings, the final diagnosis was soft tissue myxoma. CONCLUSIONS: Further studies are necessary to clarify the origin and histogenesis of this lesion.

Haemangiopericytoma of the maxillary gingiva: report of a case.

AIM: Haemangiopericytoma (HPC) represents approximately 3% of all tumours in the head and neck. This tumour is a soft tissue tumour derived from mesenchymal cells with pericytic differentiation. We present the clinicopathological findings of a case. MATERIALS AND METHODS: A 69-year-old man was referred to our Department for a mass located on the right pre-molar maxillary gingiva; this mass caused problems during chewing, but was otherwise asymptomatic. RESULTS: Clinical examination revealed a nodular, pink lesion, 3.5 cm in diameter, which was lined with normal mucosa. The lesion was mobile in relation to the deep and superficial tissues. Microscopic analysis of the neoplasm showed a vascular rich pattern, constituted by vessels covered with flat endothelium and surrounded by abundant spindly cells. On the basis of these histological and immunohistochemical findings, the final diagnosis was HPC. CONCLUSIONS: HPC is an uncommon vascular tumour for which the biological behaviour is difficult to predict. In our patient, no recurrences or distant metastases were present at a 4 years follow-up.

Spindle cell lipoma of the floor of the mouth: report of a case.

Spindle cell lipoma is a benign tumour composed by: (1) mature fat cells; (2) spindle cells; (3) a myxoid matrix separated by thick bands of birefringent collagen. Only 14 cases have been reported in the oral cavity. The authors present the second case located in the floor of the mouth. The treatment of the lesion consists of a local excision.

Genetic profiling of central giant cell granuloma of the jaws.

Central giant cell granuloma (CGCG) of the jaws is a central osteolytic lesion characterized histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. Whether CGCG is a reactive lesion or a truly benign neoplasm remains undetermined, and the mechanism determining the onset of the disease remains unknown. To have more information regarding the genetic events involved in CGCG, the authors decided to perform an expression profile. Samples were derived from two surgically resected CGCG of the mandible. RNA extracted from a pool of three normal bone tissues was used as control. By using DNA microarrays containing 19,200 genes, the authors identified several genes whose expression was significantly up- or down-regulated. The differentially expressed genes cover a broad range of functional activities: cell cycle regulation; signal transduction; and vesicular transport. It was also possible to detect some genes whose function is unknown. The authors believe the data reported to be the first genetic portrait of CGCG of the jaws. Several markers have been identified that can potentially help in identifying some biological behavior (ie, quiescent versus aggressive lesions), as well as genes whose products could be potentially disease-specific targets for therapy. However, the authors think that more cases are needed, especially those comparing quiescent and aggressive lesions, before the exact profile of CGCG is known.

Antioxidant status (CoQ10 and Vit. E levels) and immunohistochemical analysis of soft tissues in periodontal diseases.

Reactive oxygen species and antioxidant status in periodontal diseases and periodontal-related pathologies is an item of growing interest. Immunohistochemical approach may be usefully employed in the study of soft tissues affected by periodontal disease, giving valuable information on tissue morphology and vascular proliferation that depends directly on the inflammatory state. In order to study CoQ(10) and vitamin E content in healthy gingiva and in gingivitis a new adaptation to previously published methods for their determination was adopted. During gingivitis tissue displayed a large inflammatory infiltration in the lamina propria and a VEGF positive squamous epithelium. The inflammatory infiltration consisted mainly of lymphocytes, plasma cells and neutrophils. Vitamin E dramatically decreased and CoQ(10) remained unchanged despite the increased amount of cells present in the periodontally affected tissues, indicating that continuous oxidative stress which occurred in these structure affected the antioxidant pattern of the tissue.

Cyclic guanosine monophosphate role in human carcinoma pathogenesis.

In order to examine the cyclic nucleotides (cGMP) role in carcinoma growth and invasivity. We analyzed two cell lines, LSHT29 and 17GT, and tissues in patients with carcinoma and malignant tissues with (N+) and without (N-) lymph node metastases. Higher cGMP levels in pathological samples suggest a strong correlation between intracellular cGMP concentration and carcinoma progression.

Solid aneurysmal bone cyst of the mandible.

Aneurysmal bone cyst is a rare, rapidly expanding, locally destructive, and often misdiagnosed lesion. It accounts for about 1-2% of primary biopsied bone tumours. About 60-70 cases have been reported in the jaws; particularly the molar regions. Eighty percent of patients are under 20 years of age. Aneurysmal bone cyst exists as a primary or secondary lesion. It may be conventional (95%) or solid (5%). The solid variant is more difficult to recognize. The practical importance of aneurysmal bone cyst lies in the fact that it must be differentiated from malignant tumours: mainly with giant cell tumours and teleangiectatic osteosarcoma.

Genetic profiling of granular cell myoblastoma.

Granular cell tumor (GCT), or granular cell myoblastoma, is a relatively uncommon lesion of the soft tissues. It can occur in any organ, and the tongue is more often affected. GCT has unknown etiology, uncertain histogenesis, and a not always benign nature. Benign myoblastomas are the great majority, but rare malignant lesions have been reported. To have more information regarding the genetic events involved in GCT, the authors decided to perform an expression profile. A sample was derived from a surgically resected GCT of the tongue. RNA extracted from normal tongue (mucosa plus muscle) was used as control. By using DNA microarrays containing 19,200 genes, the authors identified several genes for which expression was significantly up- or down-regulated. The differentially expressed genes cover a broad range of functional activities: (1) signal transduction, (2) cell cycle regulation, and (3) cytoskeleton organization. It was also possible to detect some genes whose function is unknown. The data reported are, to the authors' knowledge, the first genetic portrait of GCT. Mutations in some of the described genes are related to neural alterations and mental diseases, and this fact supports the idea of a neural origin of myoblastoma. Several markers have been identified that will help in identifying the biological behavior (when malignant lesions will be described), as well as the gene whose products could be potentially disease-specific targets for therapy.

Expression profiling of ameloblastic carcinoma.

Ameloblastic carcinoma (AC) is a malignant epithelial odontogenic tumor that histologically retains the features of ameloblastic differentiation and exhibits cytological features of malignancy in the primary or recurrent tumor. It may develop within a preexisting ameloblastoma or arise de novo or from an odontogenic cyst. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of cell and tissue gene expression. By using DNA microarrays containing 19,200 genes, several genes whose expression was significantly upregulated or downregulated were identified in a case of AC. The differentially expressed genes cover a broad range of functional activities: 1) transcription, 2) signaling transduction, 3) cell cycle regulation, 4) apoptosis control, and 5) differentiation. The data reported are, to our knowledge, the first genetic portrait of an AC. No final conclusion can be drawn; however, this portrait will be useful in investigating the biological behavior and in identifying possible gene targets for cancer therapy when more cases of this rare tumor are reported and compared.

Cyclic AMP phosphodiesterase activity in human gingival carcinoma.

BACKGROUND: The phosphodiesterases (PDEs) are responsible for the hydrolysis of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), to their corresponding monophosphates with a fundamental role in the transduction of the intracellular signals. At least 11 different enzymatic isoforms have been identified, which are listed according to their specificity or affinity for the substratum, identity of the amino acid sequence, cofactor, and inhibitor sensitivity. Variations in PDE activity have been found in different pathologies, and they have also been correlated to different pathological e/o physiological mechanisms, such as cellular differentiation, apoptosis, and tumor invasivity. OBJECTIVES: In this study, we have evaluated cAMP PDE activity in patients with carcinoma of the gingiva, with the purpose of correlating differences in its development and progression. The same enzymatic activity has been used to evaluate differences between patients with lymph node involvement (group N(+)), and patients without lymph node involvement (N(-)). MATERIALS AND METHODS: The analysis of PDE activity and the cAMP assay was performed by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cAMP was confirmed with the enzyme-linked immunoabsorption assay (EIA). RESULTS AND CONCLUSIONS: The differences between control and N(-) groups (P = 0.0433), and between control and N(+) groups (P = 0.0156) were statistically significant. PDE3A was also evaluated immunohistochemically in lymph-node negative and lymph-node positive cases. The differences between the two groups were statistically significant (P = 0.0397).

Malignant melanoma of the maxillary gingiva: a case report.

BACKGROUND: Mucosal malignant melanoma of the of the head and neck is a rare neoplasm, accounting for about 0.2% of all melanomas. We present the clinopathological findings of a case. METHODS: An 83-year-old woman presented with a dark reddish pigmented lesion which had appeared 3 years previously. RESULTS: Clinical examination revealed a sessile lesion, 1.5 cm in diameter, located on the vestibular maxillary gingiva next to the first molar area. Microscopic analysis of the neoplasm showed epithelioid cells with prominent nucleoli aggregated in solid nests. Cytoplasmic melanin pigmentation was present. The neoplastic cells were positive for HMB-45 and S100 protein. The final histologic diagnosis was primary malignant melanoma of the gingiva. Physical examination and a computerized tomography scan of the neck, liver, and lungs ruled out the possibility of occult melanoma lesions elsewhere in the body. CONCLUSION: The prognosis for patients with oral malignant melanoma is extremely poor. Earlier recognition of this condition simplifies treatment and greatly improves the prognosis for these patients.

Calretinin expression in odontogenic cysts.

Calretinin is a calcium-binding protein with a possible role as a calcium buffer, calcium-sensor, or regulator of apoptosis. Calretinin is expressed in neural tissue, is a specific marker of mesothelial cells, and has been demonstrated in the odontogenic epithelium during odontogenesis in rat molar tooth germs. Moreover, it has been found to be expressed in a high proportion of solid, unicystic, and multicystic ameloblastomas, whereas, on the contrary, no positive staining has been found in odontogenic keratocysts, residual cysts, and dentigerous cysts. The purpose of this study was to evaluate calretinin expression in radicular cysts, follicular cysts, orthokeratinized keratocysts, and parakeratinized keratocysts. A total of 70 odontogenic cysts, 24 radicular cysts, 24 follicular cysts, and 22 odontogenic keratocysts (10 orthokeratinized keratocysts, 12 parakeratinized keratocysts) were evaluated. All the radicular cysts, follicular cysts, and orthokeratinized keratocysts were negative. However in 8 of 12 parakeratinized keratocysts, there was a positivity to calretinin in the parabasal-intermediate layers of the cyst epithelium. This positivity to calretinin in the parabasal layers in parakeratinized keratocysts, similar to that found for other markers like PCNA and p53, could point to an abnormal control of the cell cycle and could help to explain the differences in the clinical and pathologic behavior of odontogenic keratocysts, in particular the differences found between orthokeratinized keratocysts and parakeratinized keratocysts.

Genetic profile of clear cell odontogenic carcinoma.

In the head and neck region, clear cell tumors are usually derived from salivary glands, odontogenic tissues, and metastasis. The World Health Organization has classified clear cell odontogenic tumor among benign tumors, but it is now recognized as a more sinister lesion, and current opinion is that it should be designated as a carcinoma. It is characterized by aggressive growth, recurrences, and metastasis. By using complementary DNA microarrays, several genes in clear cell odontogenic tumor were identified that are differentially regulated when compared with non-tumor tissue. In conclusion, the first genetic profiling of clear odontogenic carcinoma is reported. DNA microarrays can potentially help in identifying some genes whose products could be disease-specific targets for cancer therapy as well as a tool for better classifying odontogenic tumor.