metallothionein and Salivary-Gland-Neoplasms

Adenoid cystic carcinoma (AdCC) of the salivary glands shows heterogeneous behaviour, with metastasis as a key indicator of poor prognosis. Metallothionein (MT) expression has been associated with poor prognosis of diverse neoplasms. We evaluated prognostic factors for AdCC and the role played by MT, focusing on metastatic behaviour.. We reviewed the files of the Brazilian National Institute of Cancer between 1997 and 2004, obtaining 49 cases. Fourteen tumours had metastasized during follow-up. Among these, we identified cases presenting with metastasis at patient admission as showing the poorest survival rates. MT immunostaining of the tumours was performed (using the E9 antibody), and evaluated for the parameters of proportion, intensity and distribution in tumour cells. Extent and intensity of staining, and Quickscore (a combined measure of extent and intensity), were higher in metastatic than non-metastatic tumours (for Quickscore, P = 0.044), with highest values found for cases of early metastasis. Most cases showing weak staining, and all with a predominantly cytoplasm-restricted staining pattern, were non-metastatic. Metastatic tumours of solid type received higher scores than solid non-metastatic (Intensity, P = 0.0239; Quickscore, P = 0.0481).. Our results demonstrated metastasis to be the most significant indicator of poor prognosis and deterioration for AdCC. Consistent patterns of MT expression were observed to correlate with metastatic behaviour, indicating that MT may potentially serve as a prognostic marker for AdCC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Metallothionein; Middle Aged; Prognosis; Retrospective Studies; Salivary Gland Neoplasms; Young Adult

Pleomorphic adenoma is the most common benign neoplasm of both the major and minor salivary glands. The histological features are diverse and are characterized by the involvement of epithelial-myoepithelial structures. Metallothionein is a cysteine-rich protein present in myoepithelial cells of several benign and malignant neoplasms. The function of metallothionein is associated with DNA protection, oxidative stress and apoptosis. The purpose of this study was to evaluate the expression of metallothionein in pleomorphic adenoma of the minor salivary glands. Additionally, we investigated the association of the clinicopathological features of the lesions with metallothionein, specifically its association with Bcl-2, in an attempt to evaluate the role of metallothionein in the control of apoptosis. Thirty-five cases of pleomorphic adenoma were selected and immunohistochemistry was performed for metallothionein and Bcl-2 proteins. The proteins were quantified by the Quickscore method. The samples showed epidemiological characteristics similar to those described in the literature. We did not find an association between the clinicopathological characteristics of pleomorphic adenomas and the proteins studied, but an association between metallothionein and Bcl-2 was demonstrated. The results suggest that metallothionein may have a role in the control of apoptosis in pleomorphic adenoma.

Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Male; Metallothionein; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Salivary Gland Neoplasms; Salivary Glands, Minor; Young Adult

Metallothionein (MT) is a protein that has been studied in several tumors as a prognostic factor and as a potential myoepithelial cell marker in breast cancer. The aims of this study were to assess the immunohistochemical staining of MT in adenoid cystic carcinomas of the salivary glands (ACC), and to analyze possible morphological and quantitative variations among the solid, cribriform, and tubular histological subtypes. MT was investigated in 15 cases of ACC using the immunohistochemical technique. All of the cases expressed the MT antigen. This expression was noteworthy in cells depicting myoepithelial differentiation. ACC with predominant tubular pattern presented a significantly lower mean index of MT immunopositivity than did solid or cribriform subtypes, while these two latter groups did not differ in terms of MT expression. Our results suggest that MT may be an important tool for immunolocalization of myoepithelial tumor cells in salivary gland neoplasms.

Topics: Adult; Aged; Carcinoma, Adenoid Cystic; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Male; Metallothionein; Middle Aged; Neoplasm Proteins; Salivary Gland Neoplasms; Salivary Glands

Expression of metallothionein (MT) in 75 cases of salivary gland tumors was studied by immunohistochemistry. All tumors containing myoepithelial cells were positive for MT immunostaining. In the tumors composed of both adenoepithelial cells and myoepithelial cells, only myoepithelial cells were MT positive. A rather large portion of cells was noted MT positive in myoepithelial carcinoma and myoepithelioma. Compared with S-100 and smooth muscle actin (SMA) antibodies, the effect of staining by MT antibody for myoepithelial cells was more satisfactory. The results indicate that MT may be a better marker for neoplastic myoepithelial cells and useful in the differential diagnosis of salivary gland tumors.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Adenoid Cystic; Humans; Metallothionein; Myoepithelioma; Salivary Gland Neoplasms

Ductal basal cells and myoepithelial cells (MEC) of normal salivary gland share metallothionein (MT)-positivity, while PTHrP positivity is restricted to ductal basal cells. We studied 21 benign and 4 malignant tumours in which MEC are thought to play a role using immuno-histochemical methods for detecting the presence of MT and PTHrP positive cells. In benign tumours, a shared positivity for MT and PTHrP is found in the inner layer of tubulo-ductal and trabecular structures, in part of the cells in the myxoid and chondroid matrices of pleomorphic adenoma, and in the basal epithelial lining of Warthin's tumours. In myoepithelioma almost all tumour cells demonstrate MT reactivity and a restricted positivity for PTHrP. MT-positive cells in oncocytoma were demonstrated in the periphery of some oncocytic islets, while PTHrP positivity was restricted to a few oncocytic cells. In malignant tumours, positivity for MT is found in the periphery of epithelial clusters of mucoepidermoid carcinomas, while PTHrP-positive cells are seen in cyst-like structures and scattered cells in solid arrangements of squamous cells. Although the biologic significance of the presence of MT in neoplastic cells is not yet clearly understood, MT may be necessary for the growth and differentiation in actively growing cells. The variability of MT expression in salivary gland tumours could be a reflection of the morphological heterogeneity and correlate with the degree of differentiation and maturation of the tumour cells. The observations suggest that MT may be considered an oncodevelopmental product.

Topics: Cell Differentiation; Cell Division; Humans; Hypercalcemia; Metallothionein; Parathyroid Hormone; Salivary Gland Neoplasms