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Abstract: This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase-2,-9 (MMP-2, MMP-9), tissue inhibitor-1 of matrix metalloproteinase (TIMP-1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship (P<0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6, HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage (P<0.01). There was also a trend of MMP-2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence (P<0.05). The expression of TIMP-1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratinizing SCC than that in basaloid SCC (P<0.05). These findings suggested that MMP-2 and MMP-9, HER2/neu and MMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.

[1]Akiyama,T., Sudo, S., Ogawara, H., Toyoshima, T. and Yamamoto, T., 1986. The product of the human c-erbB2 gene: A 185-kilodalton with tyrosine kinase activity. Science, 323: 1644-1646.

[2]Bahar, R., Kunishi, M., Kayada, Y. and Yashigo, K., 1997. CD44 variants 6 (CD44v6) expression as a progression marker benign, premalignant and malignant oral epithelial tissues. Int J Oral Maxillofac, 26: 443-446.

[3]Baybaud-Diogene, H., Tetu, B., Morency, R., Fortin, A. and Monteil, R.A.,1996. P53 overexpression in Head and Neck Squamous Cell Carcinoma: Review of the literature. Orol Oncol, Eur J Cancer, 32B: 143-149.

[4]Brummer, O., Athar, S., Riethdorf, L., Loning, T. and Herbst, H., 1999. Matrix-metalloproteinase 1, 2, and 3 and their tissue inhibitors 1and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch, 435: 566-573.

[5]Chomchai, J.S., Du, W., Sarkar, F.H., Li, Y.W., Jacobs, J.R., Ensley, J.E., Sakr,W. and Yoo,G.H., 1999. Prognostic significance of p53 gene mutations in laryngeal cancer. Laryngoscope, 109: 455-459.

[6]Curran, S. and Murray, G.I., 2000. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur of Cancer, 36: 1621-1630.

[7]Guthert,U., Hofmann, M., Rudy, W., Reber, S., Zoeller, M., Haussmann, I., Matzku,S., Wenzel, A., Ponta, H. and Herrlich, P., 1991. A new variant of glycoprotein CD44 confers metastastic potential to rat carcinoma cells. Cell, 65: 13-24.

[8]Hong, S.D., Hong, S.P., Lee, J.I. and Lim, C.Y., 2000. Expression of matrix metalloproteinase-2, and -9 in oral squamous cell carcinomas with regard to the metastatic potential. Oral Oncology, 36: 207-213.

[9]Liotta, L.A., 1986. Tumor invasion and metastases-role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res., 46: 1-7.

[10]Lupu, R., Cardillo, M., Harris, L., Hijazi, M. and Rosenberg, K., 1987. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science, 235: 177-182.

[11]Merz, H., Malisius, R., Mannweiler, S., Zhou,R., Hartmenn, W., Orscheschek, K., Moubayed, P. and Feller, A.C., 1995. Methods in laboratory investigation immunoMax: a maximized immunohistochemical method for the retrieval and enhancement of hidden antigens. Laboratory Investigation, 73: 149-156.

[12]Miyajima, J., Nakano, R. and Morimatsu, M., 1995. Analysis of expression of matrix metalloproteinases-2 and -9 in hypopharyngeal squamous cell carcinoma by in situ hybridization. Ann Oto Rhino Larygol, 104: 678-684.

[13]O-charoentat, P., Modjtahedi, H., Rhys-Evans, P., Court, WJ., Box, G.M. and Eccless, A., 2000. Epidermal growth factor-like ligands differentially upregulate matrix metalloproteinase-9 in head and neck squamous cell carcinoma. Cancer Res., 60:1121-1128.

[14]Ornstein, D.L., Macnab, J. and Cohn, K.H., 1999. Evidence for tumor host cooperation in regulating MMP-2 expression in human colon cancer. Clin Exp Metastasis, 17: 205-212.

[15]Ostwarld, J., Pracht, O., Rhode, E. and Kramp, B., 1997. Are the products of CD44 exons v5 and v6 markers for metastasis of laryngeal carcinomas Laryngorhinootologie, 76:295-299.

[16]Overall, C.M., 1994. Regulation of tissue inhibitor of matrix metalloproteinase expression, Inhibition of matrix metalloproteinases. Ann NY Acad Sci, 732: 51-67.

[17]Parker, S.L., Tong, T., Bolden, S. and Wingo, P.A., 1997. Cancer statistic, CA Cancer. J Clin, 47: 5-27.

[18]Polette, M., Clavel, C., Birembaut, P. and De Clerck,Y.A., 1996. Localization by in situ hybridization of mRNAs encoding stromelysin 3, tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 and head and neck carcinoma. Pathol Res Pract, 189: 1052-1057.

[19]Ro, J., EI-Naggar, A., Ro, J.Y., Blick, M., Frye, D., Fraschini, G., Fritsch, H. and Hortobagyi, G., 1989. C-erbB-2 amplification in node-negative human breast cancer. Cancer Res, 49: 6941-6944.

[20]Tan, M., Yao, J. and Yu, D.,1997. Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. Cancer Res, 57: 1199-1205.

[21]Tantaway, A., Louins, L. and Hamza, M.,1999. Expression of c-erbB-2 oncoprotein in cancer of the larynx in relation to invasion of the cartilagenous framework and prognosis. Eur Arch Otorhinolaryngol, 256: 72-77.

[22]Theillet, C., 1993. P53 genes and solid tumors. Bull Cancer, 80: 693-6.

[23]Vermeulen, P.B., Roland, L., Mertens, V., Van Marck, E., De Bruijn, E.A., Van Oosterom, A.T. and Dirix, L.Y., 1996. Correlation of intratumoral microvessel density and p53 protein overexpression in human colorectal adenocarcinoma. Microvasc Res, 51: 164-174.

[24]Weinstein, G.S., Nuamah, I.F. and Tucker, J., 1996. Moutone K: Evaluation of HER2/neu (c-erbB-2) oncogene expression in organ sections of supraglottic squamous cell carcinoma. Ann Oto Rhinol Laryngol, 105: 275-279.

[25]Xia, W., Lau, Y.K., Zhang, H.Z., Lin, A.R., Lin, L., Kiyokawa, N., Clayman, G.L. and Katz, R.L., 1997. Strong correlation between c-erbB-2 overexpression and overall survival of patients with oral squamous cell carcinoma. Clin Cancer Res, 3: 3-9.

[26]Yu, Q. and Stamenkovic, I., 1999. Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Gene and Development, 13:35-38.