Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvß3 in mucoepidermoid carcinoma and acinic cell adenocarcinoma of salivary gland origin.

OBJECTIVE: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvß3 in pleomorphic adenoma (PA), acinic cell adenocarcinoma (ACA), and mucoepidermoid carcinoma (MEC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the levels of expression of OPN and its receptors in normal salivary glands (NSG) (n = 20), PA (n = 20), ACA (n = 11), and MEC (n = 29). RESULTS: OPN expression was increased in ACA and MEC compared with PA and NSG (median scores, 6, 6, 4, and 4, respectively). CD44 expression was increased in ACA and reduced in MEC and PA compared with NSG (median scores, 8, 4, 3, and 5, respectively). Integrin αvß3 median scores were 5 in ACA, 1 in MEC, and 0 in PA and NSG. CONCLUSIONS: OPN is expressed in salivary gland tumors and is at higher levels in ACA and MEC.

Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvß3 in pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma.

OBJECTIVES: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvß3 in pleomorphic adenoma (PA), polymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcinoma (ACC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the level of expression of OPN and its receptors in normal salivary glands (NSG; n = 20), PA (n = 20), PLGA (n = 16), and ACC (n = 22). RESULTS: OPN expression was increased in PLGA and intermediate-/high-grade ACC compared with PA and NSG (median scores, 6, 5, 4, and 4, respectively). CD44 expression was reduced in PA, PLGA, and ACC. OPN expression levels were moderately correlated with CD44 in PLGA. Integrin αvß3 was not expressed in PA and ACC and was seen in only 1 case of PLGA. CONCLUSIONS: OPN is expressed in salivary gland tumors but does not correlate well with CD44 and αvß3.

TGF-ß1 and FAK regulate periostin expression in PDL fibroblasts.

Recently identified as a key component of the murine periodontal ligament (PDL), periostin has been implicated in the regulation of collagen fibrillogenesis and fibroblast differentiation. We investigated whether periostin protein is expressed in the human PDL in situ and the mechanisms regulating periostin expression in PDL fibroblasts in vitro. With immunohistochemistry, periostin protein was identified in the PDL, with expression lower in teeth with reduced occlusal loading. In vitro application of uniaxial cyclic strain to PDL fibroblasts elevated periostin mRNA levels, depending on the age of the patient. Treatment with transforming growth factor-beta1 (TGF-ß1) also significantly increased periostin mRNA levels, an effect attenuated by focal adhesion kinase (FAK) inhibition. FAK-null fibroblasts contained no detectable periostin mRNA, even after stimulation with cyclic strain. In conclusion, periostin protein is strongly expressed in the human PDL. In vitro, periostin mRNA levels are modulated by cyclic strain as well as TGF-ß1 via FAK-dependent pathways.

Human kallikrein 3 (prostate specific antigen) and human kallikrein 5 expression in salivary gland tumors.

The human kallikrein 5 protein (hK5) is expressed in many normal tissues, most notably in skin, breast, salivary gland and esophagus. It has also been shown to be a potential biomarker for breast, ovarian and testicular cancer. Human kallikrein 3 (hK3; prostate-specific antigen) is the most useful marker for adenocarcinoma of the prostate gland. The aim of this study was to determine whether hK3 and hK5 are expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors do not show high levels of expression of hK5. Staining was most prominent in keratinizing epithelia in pleomorphic adenomas. hK3 is not expressed in salivary gland tumors.

Human kallikrein 13 expression in salivary gland tumors.

The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.

Peripheral ameloblastic fibroma.

Peripheral ameloblastic fibroma is an exceedingly rare lesion. Only three reports could be found, two of which appeared in the Japanese literature. Here, we report a case of peripheral ameloblastic fibroma occurring in a 5-year-old girl. The diagnosis was made after careful microscopic examination, to exclude other lesions. The lesion was excised and has not recurred 1 year after removal.

Osteopontin expression in salivary gland tumours.

Osteopontin (OPN) is expressed in numerous carcinomas and plays a role in tumour development, invasion and metastasis. This study examines by immunohistochemistry the expression of OPN in normal salivary gland tissue and three types of salivary gland tumour: pleomorphic adenoma (PA), adenoid cystic carcinoma (ACC) and polymorphous low grade adenocarcinoma (PLGA). PAs and PLGAs demonstrated higher levels of OPN than normal salivary gland tissue, while ACC, although showing a trend towards increased OPN, was not significantly different. The results of this study indicate that OPN expression is present in normal salivary gland tissue, and is increased in certain salivary gland tumours, but further investigation is necessary to clarify its role.

Human kallikrein 6 expression in salivary gland tumors.

Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied.

Osteosarcoma of the jaws in children.

Two cases of osteosarcoma of the jaws in children are reported. One patient was a 13-year-old girl whose first symptoms included nasal and maxillary sinus congestion, followed by epistaxis. She was found to have chondroblastic osteosarcoma extending through the left maxillary alveolar process and sinus. Following surgery and chemotherapy, the patient has been free of disease for 7 years. The second patient, an 8-year-old boy, was diagnosed with juxtacortical (parosteal) osteosarcoma of the mandible, which is a less aggressive variant of the neoplasm. It is believed that this is the youngest patient reported to date with juxtacortical osteosarcoma of the jaws. He was treated by block resection of the right side of the mandible and is free of disease 3(1/2) years later.

Metallothionein in human gingival amalgam tattoos.

Amalgam tattoos occur when small particles of dental amalgam, composed largely of silver (Ag) and mercury (Hg), are inadvertently implanted into oral soft tissues during dental procedures. Metallothioneins (MTs) are ubiquitous, low molecular weight, cysteine-rich, metal-binding proteins that are inducible by many agents including metals and may be involved in the detoxification of toxic metals such as Hg. In this study, the correlation between MT expression and amalgam tattoos in human gingiva was investigated using energy-dispersive X-ray microanalysis (EDX) and immunohistochemical techniques. Light microscopically, amalgam tattoos presented as either fine granular particles or larger discrete opaque globular particles in connective tissues. EDX revealed the smaller particles to be silver sulphide (Ag(2)S), while the larger particles exhibited a shell of Ag(2)S that contained irregularly distributed masses of Ag and Hg. Particles of tin (Sn) were also found. No MT staining was observed in collagen, fibroblasts or blood vessels in areas exhibiting abundant amounts of embedded fine granular Ag(2)S particles. Blood vessels exhibiting relatively few amalgam particles stained positively for MT. Cells with the morphological features of histiocytes located directly adjacent to larger pieces of amalgam showed intense MT staining. These results indicate that amalgam tattoos contain no Hg or free Ag except in large globular pieces of amalgam, which still contain Hg and which induce MT expression in adjacent histiocytes. This suggests that Hg leaching from impacted dental amalgam particles induces MT, while residual Ag(2)S and Sn particles do not. MT may therefore act to reduce Hg exposure in patients with amalgam tattoos.

Immunohistochemical localization of fibroblast growth factors FGF-1 and FGF-2, and receptors FGFR2 and FGFR3 in the epithelium of human odontogenic cysts and tumors.

Acidic (FGF-1) and basic (FGF-2) fibroblast growth factors are members of a family of growth factors that function in growth, differentiation and regeneration of a variety of tissues. Their presence in human odontogenic cysts and tumors has not been previously investigated. This study was designed to detect immunohistochemically the presence of these factors and two fibroblast growth factor receptors (FGFR2 and FGFR3) in a cross section of odontogenic cysts and tumors, to determine if they may be involved in the differentiation of odontogenic epithelium or, more specifically, in the development of particular cysts or tumors. Archival formalin-fixed paraffin-embedded tissues were used. With some exceptions, FGF-2 and the receptor FGFR2, were found in the cytoplasm and occasionally in the nuclei of cells of odontogenic epithelium, while FGF-1 and the receptor FGFR3, were absent or only focally or weakly detected, using standard immunohistochemical techniques. The data are similar to those published for normal murine odontogenesis, suggesting that these factors are associated with odontogenic differentiation rather than pathogenesis. The presence of significant nuclear staining in odontogenic epithelium associated with embryonic mesenchyme in ameloblastic fibromas and ameloblastic fibro-odontomas suggests that FGF-2 may be involved in directing nuclear activity at the histodifferentiation stage of odontogenesis.

Common salivary gland disorders: an update.

Disorders of the salivary glands range from common inflammatory and functional conditions, to rare types of neoplasms. An overview and update of selected, common non-neoplastic and neoplastic conditions is presented.

Foreign body gingivitis: clinical and microscopic features of 61 cases.

Gingival inflammation associated with foreign bodies in connective tissue is termed foreign body gingivitis. It is not recognized commonly by clinicians and has not been described fully in the literature. This study examined the clinical and microscopic features of 61 cases of foreign body gingivitis. It was more common in women and occurred at a mean age of 48 years. It presented most frequently as a red or red and white painful chronic lesion that had been present for less than 1 year. Often it was diagnosed clinically as lichen planus. There was no gingival site predilection. Microscopically, foreign bodies, usually less than 5 microns in diameter, were found in an area of moderate to severe inflammation composed of lymphocytes, histiocytes, and plasma cells. The inflammation frequently was granulomatous and sometimes lichenoid.

Foreign body gingivitis: identification of the foreign material by energy-dispersive x-ray microanalysis.

Foreign bodies identified in 61 cases of foreign body gingivitis were analyzed by energy-dispersive x-ray microanalysis. This was compared with the energy-dispersive x-ray microanalysis of 62 dental materials. Comparative analysis indicated most foreign bodies were of dental material origin, usually abrasives. It is suggested that they are factitially and iatrogenically introduced during a variety of self-administered and professionally performed dental hygiene and restorative procedures. Individual elements, and elements by class, were correlated with previously described clinical and microscopic features of the cases. There was no association between any microscopic or clinical attribute of FBG and the presence of allergenic or cytotoxic elements. It is postulated that the physical presence of foreign bodies may be sufficient for the development of foreign body gingivitis. Dentists should be aware of the potential for chronic tissue damage that can result from the unguarded use of abrasive material next to the gingiva.

Atypical cartilage in reactive osteocartilagenous metaplasia of the traumatized edentulous mandibular ridge.

Eighteen cases of reactive osteocartilagenous metaplasia of the edentulous mandibular alveolar ridge forming clinical masses that mimic neoplasms are reported. Although most of these lesions appeared histologically benign, three exhibited atypical microscopic features suggestive of chondrosarcoma. Of those cases that were followed, none of the lesions recurred after simple surgical excision. Because many investigators consider all cartilagenous lesions of the jaws potentially malignant, the importance of recognizing this benign condition is stressed.

Schwann cell differentiation of modified myoepithelial cells within adenoid cystic carcinomas and polymorphous low-grade adenocarcinomas: clinicopathologic assessment of immunohistochemical staining.

Adenoid cystic carcinomas and polymorphous low-grade adenocarcinomas have a known propensity for perineural invasion. Although modified myoepithelial cells have been shown to possess characteristics of a variety of cell types, they have not yet been found to mimic nerve tissue. Histologic evidence of Schwann cell differentiation would suggest the pathophysiologic mechanism by which these tumours exhibit neurotropism. An archival study of 41 specimens was performed to evaluate the Schwann cell staining properties of adenoid cystic and polymorphous low-grade adenocarcinomas using antibodies to S-100 protein, GFAP, neuron-specific enolase, and using a solochrome stain. Charts were reviewed to assess correlations between immunohistochemical and histochemical staining properties and various clinical parameters. The findings strongly suggest that neuronal differentiation does occur within these tumours. Furthermore, it was determined that solochrome positivity confers a significantly less favourable disease-free interval in these neoplasms. This new finding was highly statistically significant and has potential implications in the determination of prognosis for patients with these tumours.

Osteopathia striata, short stature, cataracts, and microdontia: a new syndrome? A case report.

A case of osteopathia striata, childhood cataracts, short stature, elbow deformity, and microdontia with rhizomicry in a white male is reported. The report includes a detailed analysis of dental changes. The relationship of this syndrome to other similar conditions including osteopathia striata with cranial base sclerosis and Rothmund-Thomson syndrome are discussed.

Salivary gland duct involvement in oral epithelial dysplasia and squamous cell carcinoma.

The clinical implications and prognostic significance of oral dysplastic or cancerous epithelium involving salivary gland ducts have not been previously investigated. Screened routine tissue sections of 1216 cases of oral epithelial dysplasias and squamous cell carcinomas revealed 26 examples (2.14%) that exhibited unequivocal ductal involvement. Ductal involvement was more likely to occur in floor of mouth lesions and in lesions exhibiting severe dysplasia or carcinoma in situ. Clinical follow-up on 23 cases showed that the recurrence rate of the preinvasive lesions that exhibited ductal involvement was equal to that of the squamous cell carcinomas. The depth of ductal dysplasia did not correlate with recurrence rate. These results suggest that the involvement of salivary gland ducts by oral epithelial dysplasias and carcinomas in situ is an uncommon but significant finding. Surgical stripping or ablation of such lesions should extend at least 3 mm below the surface to ensure eradication of these reservoirs of dysplastic cells.

Exfoliative cheilitis.

Exfoliative cheilitis is an uncommon condition affecting the vermilion zone of the upper, lower or both lips. It is characterized by the continuous production and desquamation of unsightly, thick scales of keratin; when removed, these leave a normal appearing lip beneath. The etiology is unknown, although some cases may be factitious. Attempts at treatment by a wide variety of agents and techniques have been unsuccessful. Three patients with this disease are reported and its relationship to factitious cheilitis and candidal cheilitis is discussed.