Nagel H, Laskawi R, Eiffert H, Schlott T
Department of Cytopathology, Georg-August-University of Göttingen, Robert-Koch-Straszligbeta;e 40, D-37075 Göttingen, Germany.
Mol Pathol. 2003 Aug;56(4):226-31. doi: 10.1136/mp.56.4.226.
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.
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.
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.
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.
人类肿瘤发生和恶性转化过程中涉及的分子遗传变化是癌症诊断和治疗的新靶点。本研究旨在分析假定的肿瘤抑制基因FHIT和WT-1以及肿瘤排斥基因BAGE、GAGE-1/2、MAGE-1、MAGE-3和HAGE(据报道在人类癌症中很重要)在涎腺肿瘤中的表达。
通过逆转录聚合酶链反应(RT-PCR)分析正常涎腺组织以及44例良性和恶性涎腺肿瘤中的基因表达。
在38例正常涎腺组织中的1例、28例腺瘤中的3例和16例癌中的2例发现了异常的FHIT转录本。在2例腺瘤和5例癌中可检测到WT-1 mRNA。免疫印迹显示WT-1 mRNA表达与WT-1蛋白浓度升高相关。检测BAGE、GAGE和MAGE基因表达的RT-PCR在2例腺瘤和9例癌中呈阳性,但在正常涎腺组织中呈阴性。在2例正常涎腺组织、11例良性肿瘤和8例恶性肿瘤中发现了HAGE mRNA。
FHIT mRNA剪接似乎不参与涎腺肿瘤的发生。上皮/肌上皮表型肿瘤中WT-1 mRNA的上调可能意味着WT-1在这些涎腺肿瘤的发生和/或细胞分化中具有潜在作用。肿瘤排斥基因在恶性涎腺肿瘤中的表达比良性肿瘤更频繁,但并非唯一,尽管没有一个适合作为涎腺肿瘤恶性程度的诊断标志物。