Prognostic Impact of Molecular Analyses in Adenoid Cystic Carcinomas of the Salivary Gland

Abstract

Background: Adenoid cystic carcinoma (ACC) of the salivary gland is a generally slow-growing but highly malignant neoplasm with a remarkable capacity for recurrence. Prognosis is greatly influenced by the histological subtype (tubular, cribriform or solid), presence of tumour at the margins, anatomic size, and lymph node metastases. However, none of these parameters has proven to be an unequivocal predictor of disease activity. Therefore, the current study was undertaken to investigate the prognostic value of molecular markers. Patients and Methods: Samples from 22 patients, including 4 patients with recurrent disease, were included in the study. By means of immunohistochemistry, the staining pattern of p53, bcl-2, P-glycoprotein, glutathione S-transferase, and topoisomerase as well as sequence analyses of p53 were performed. These molecules were chosen because of their proven association with poor prognosis and therapy resistance in other malignancies. Results: Homozygous p53 mutations were found in all of the 4 recurrent tumors. The other proteins were detected in some tumors, but showed no correlation with histological subtype or recurrence of tumor. Conclusion: The results of the current study emphasize the prognostic value of a p53 alteration as an independent prognostic marker. Further, it could be demonstrated for the first time that proteins known for their association with radio- and chemotherapy resistance can be overexpressed in some ACCs suggesting that those molecules could influence the outcome of new therapeutical approaches.