Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry

• Published in: Histopathology 2003-04, Vol.42 (4), p.348-356
• Main Authors: Skálová, A, Stárek, I, Vanecek, T, Kucerová, V, Plank, L, Szépe, P, Di Palma, S, Leivo, I
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; c-erbB-2; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - secondary; Female; FISH; Gene Amplification; Gene Expression - genetics; Genes, erbB-2; HER-2/neu; Humans; Immunoenzyme Techniques; immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Medical sciences; Middle Aged; Otorhinolaryngology. Stomatology; Parotid Neoplasms - genetics; Parotid Neoplasms - metabolism; Parotid Neoplasms - pathology; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; salivary duct carcinoma; Salivary Ducts - pathology; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1046/j.1365-2559.2003.01600.x

Aims:  Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER‐2/neu oncogene and over‐expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER‐2/neu using immunohistochemistry (IHC) has shown over‐expression in most cases. However, correlation between IHC and molecular genetic analysis of HER‐2/neu in salivary duct carcinoma has not yet been performed. Methods and results:  We have now evaluated 11 cases of salivary duct carcinomas for HER‐2/neu status using IHC and fluorescent in‐situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER‐2/neu in salivary duct carcinoma. Conclusions:  In immunohistochemistry, over‐expression of HER‐2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER‐2/neu gene by means of FISH analysis. Both amplified and non‐amplified salivary duct carcinomas with strong immunohistochemical staining for HER‐2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER‐2/neu protein over‐expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over‐expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over‐expression of HER‐2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.