Analysis of the tumour suppressor genes, FHIT and WT-1, and the tumour rejection genes, BAGE, GAGE-1/2, HAGE, MAGE-1, and MAGE-3, in benign and malignant neoplasms of the salivary glands.
OBJECTIVE
Molecular genetic changes involved in tumorigenesis and malignant transformation of human tumours are novel targets of cancer diagnosis and treatment. This study aimed to analyse the expression of putative tumour suppressor genes, FHIT and WT-1, and tumour rejection genes, BAGE, GAGE-1/2, MAGE-1, MAGE-3, and HAGE (which are reported to be important in human cancers), in salivary gland neoplasms.


METHODS
Gene expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) in normal salivary gland tissue and 44 benign and malignant salivary gland tumours.


RESULTS
Aberrant FHIT transcripts were found in one of 38 normal salivary glands, three of 28 adenomas, and two of 16 carcinomas. WT-1 mRNA was detectable in two adenomas and five carcinomas. Immunoblotting showed that WT-1 mRNA expression was associated with raised WT-1 protein concentrations. RT-PCR for detection of BAGE, GAGE, and MAGE gene expression was positive in two adenomas and nine carcinomas, but negative in normal salivary gland tissue. HAGE mRNA was found in two normal salivary glands, 11 benign, and eight malignant tumours.


CONCLUSIONS
FHIT mRNA splicing does not appear to be involved in the genesis of salivary gland neoplasms. The upregulation of WT-1 mRNA in tumours of epithelial/myoepithelial phenotype may imply a potential role of WT-1 in the genesis and/or cellular differentiation of these salivary gland tumours. The tumour rejection genes were more frequently, but not exclusively, expressed in malignant salivary gland tumours than in benign neoplasms, although none was suitable as a diagnostic marker of malignancy in salivary gland neoplasms.
Nagel
H
H
Department of Cytopathology, Georg-August-University of Göttingen, Robert-Koch-Straszligbeta;e 40, D-37075 Göttingen, Germany. hnagel@med.uni-goettingen.de
Laskawi
R
R
Eiffert
H
H
Schlott
T
T
D017766:Acid Anhydride Hydrolases; D000230:Adenocarcinoma / Q000235:genetics; D008949:Adenoma, Pleomorphic / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D018267:Carcinoma, Acinar Cell / Q000235:genetics; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D003537:Cystadenoma / Q000235:genetics; D053487:DEAD-box RNA Helicases; D004265:DNA Helicases; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D058950:Melanoma-Specific Antigens; D009208:Myoepithelioma / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D010157:Palatal Neoplasms / Q000235:genetics; D010307:Parotid Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D000951:Antigens, Neoplasm; D053487:DEAD-box RNA Helicases; D004265:DNA Helicases; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D025721:WT1 Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C092706:BAGE protein, human; C095365:GAGE1 protein, human; C095366:GAGE2A protein, human; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C412324:DDX43 protein, human