The Gene Expression Study Of The Epithelial Membrane Protein 1 And Matrix Mettallo-proteinases In Laryngeal Squamous Cell Carcinomas And Clinical Applications

OBJECTIVETo investigate the role of expression of the epithelial membrane protein 1 (EMP-1) and matrix mettallo-proteinases (MMP20, MMP3, MMP14 and MMP24) in laryngeal carcinogenesis and the relationship between their expression, the laryngeal biological behavior and the prognosis. METHODSThe differential gene expression between laryngeal squamous cell carcinoma and its corresponding normal mucosa was analysed by microarray analysis. The gene expression of EMP-1, MMP20, MMP3, MMP14 and MMP24 in fresh laryngeal cancer tissues and their corresponding normal mucosas was detected by RT-PCR. The expression of MMP20, MMP3 and MMP14 proteins in paraffin-embedded tissues was determined immunohistochemically.All statistical analyses were performed by SPSS version 10.0. RESULTS(1) A cDNA microarray analysis consisting of 11431 human genes revealed significant changes in the expression of 35 genes, with 8 genes being up-regulated and 27 being down-regulated. EMP-1 is one of the down-regulated genes. The EMP-1 mRNA level in all laryngeal carcinoma cells was significantly lower than that in the matched primary normal epithelial cells (P<0.05) and was not correlated to the stage and differentiation of laryngeal carcinoma (p>0.05).(2) In the 36 cases of matched specimens, MMP20 gene expression was much higher in tumor tissues than that in corresponding normal tissues in 5 cases, whereas in other 31 cases, no significant difference was observed between the cancer tissue and the corresponding normal tissue. 73 cases of paraffin-embedded laryngeal cancer samples with corresponding normal tissue were detected immunohistochemically, and it was shown that MMP20 protein was localized predominantly in the tumor cell cytoplasm in 68 cases and nucleus in 5 cases. MMP20 protein was weakly or not expressed in normal tissue. MMP20 protein was over-expressed in most of the laryngeal cancers. The MMP20 protein differential expression level is significantly higher in the carcinomas with lymph node metastasis than those without metastasis (p=0.023). The MMP20 protein expression in nucleus may correlate to the invasion and metastasis of laryngeal cancer.(3) In the 33 cases of matched specimens, MMP3 gene expression was much higher in tumor tissues than that in corresponding normal tissues in 30 cases, whereas in other 3 cases, no significant difference was observed between the cancer tissues and the corresponding normal tissues. There was no correlation between MMP3 gene expression and the stage, differentiation, and lymph node metastasis of the laryngeal cancers (p>0.05). 67 cases of paraffin-embedded laryngeal cancer specimens with corresponding normal tissue were analysed...