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http://dx.doi.org/10.7314/APJCP.2013.14.9.5301

Relationships Between Clinical Behavior of Laryngeal Squamous Cell Carcinomas and Expression of VEGF, MMP-9 and E-Cadherin  

Akdeniz, Onder (Department of Otorhinolaryngology, Bursa SevketYilmaz Training and Research Hospital)
Akduman, Davut (Department of Otorhinolaryngology, Bursa SevketYilmaz Training and Research Hospital)
Haksever, Mehmet (Department of Otorhinolaryngology, Bursa SevketYilmaz Training and Research Hospital)
Ozkarakas, Haluk (Department of Otorhinolaryngology, Acibadem University, Kadikoy Acibadem Hospital)
Muezzinoglu, Bahar (Department of Pathology, Kocaeli University, School of Medicine)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.9, 2013 , pp. 5301-5310 More about this Journal
Abstract
The biological mechanisms of cancer and associations with behavior of tumours need to be studied to understand progression and determine appropriate treatments. Here we investigated expression of VEGF, MMP-9 and E-cadherin in laryngeal SCCs and their relations with clinical behavior. This prospective study was based on 38 surgical specimens from patients with primary laryngeal SCC and data recorded in their cards. Expression of the three factors in tumor tissue was examined using immunohistochemistry and correlations with clinical parameters of primary tumors, regional lymph node metastases, stage of disease, histopathologic differentiation, and vascular/cartilage invasion were investigated. Regarding the cases with positive MMP-9 expression, the difference between well and moderately/poorly differentiated tumors was statistically significant. However, differences between early stage (stage I and II) and late-stage (stage III and IV) tumours, and between positive and negative for pLN metastasis were not. No significant relationship between positive VEGF and tumor differentiation or stage was apparent, but E-cadherin levels significantly differed between well and moderately/poorly differentiated tumours and with the presence of pLN metastasis. E-cadherin staining did not vary between MMP-9 positive and negative cases. In conclusion, MMP-9 may be a negative predictor of differentiation in laryngeal SCC, while E-cadherin is a predictor of differentiation and nodal metastases. Even if the difference between VEGF expression and tumor stage was not statistically significant, it seems that there exists some relationship, which might be clarified with a greater number of cases.
Keywords
Laryngeal squamous cell carcinoma; MMP-9; VEGF; E-cadherin; metastases; prognosis;
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1 Charous SJ, Stricklin GP, Nanney LB, Netterville JL, Burkey BB (1997). Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in head and neck squamous cell carcinoma. Ann Otol Rhinol Laryngol, 106, 271-8.   DOI
2 Colovic Z, Pesutic-Pisac V, Poljak NK, et al (2013). Expression of matrix metalloproteinase-9 in patients with squamous cell carcinoma of the larynx. CollAntropol, 37, 151-5.
3 Dutta A, Sen T, Chatterjee A (2010). All-trans retinoic acid (ATRA) downregulates MMP-9 by modulating its regulatory molecules. Cell Adh Migr, 4, 409-18.   DOI   ScienceOn
4 Eidelman S, Damsky CH, Wheelock MJ, Damjanov I (1989). Expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in normal human tissues and tumors. Am J Pathol, 135, 101-10.
5 Ferrara N, Davis-Smyth T (1997). The biology of vascular endothelial growth factor. Endocr Rev, 18, 4-25.   DOI
6 FrigugliettI CU, Mello ES, Castro IV, Filho GB, Alves VA (2000). Metalloproteinase-9 immunoexpression and angiogenesis in thyroid follicular neoplasms: relation to clinical and histopathologic features. Head Neck, 22, 373-9.   DOI
7 Gupta K, Kshirsagar S, Li W, et al (1999). VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res, 247, 495-504.   DOI   ScienceOn
8 Frixen UH, Behrens J, Sachs M, et al (1991). E-cadherinmediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol, 113, 173-85.   DOI
9 Folkman J (1990). What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst, 82, 4-6.   DOI
10 Gerrow K, El-Husseini A (2006). Cell adhesion molecules at the synapse. Front Biosci, 11, 2400-19.   DOI
11 Haksever M, Inancli HM, Tuncel U, et al (2012). The effects of tumor size, degree of differentiation, and depth of invasion on the risk of neck node metastasis in squamous cell carcinoma of the oral cavity. Ear Nose Throat J, 91, 130-5.
12 Hermanek P, Sobin LH (1997). UICC TNM Classification Of Malignant Tumors, 5th ed. New York, John Wiley
13 Hiraki A, Shinohara M, Ikebe T, et al (1996). Immunohistochemical staining of desmosomal components in oral squamous cell carcinomas and its association with tumour behaviour. Br J Cancer, 73, 1491-7.   DOI
14 Hong SD, Hong SP, Lee JI, Lim CY (2000). Expression of matrix metalloproteinase-2 and-9 in oral squamous cell carcinomas with regard to the metastatic potential. Oral Oncol, 36, 207-13.   DOI   ScienceOn
15 Howlader N, Noone AM, Krapcho M, et al (2011). National Cancer Institute. Bethesda, MD. based on November 2011 SEER data submission, posted to the SEER web site, April 2012.
16 Jakobsson PA, Eneroth CM, Killander D, Moberger G, Martensson B (1973). Histologic classification and grading of malignancy in carcinoma of the larynx. Acta Radiol Ther Phys Biol, 12, 1-8.   DOI
17 Kim KJ, Li B, Winer J, et al (1993). Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature, 362, 841-4.   DOI   ScienceOn
18 Jakobsson PA (1975). Histologic grading of malignancy and prognosis in glottic carcinoma of the larynx. Can J Otolaryngol, 4, 885-92.
19 Kaomongkolgit R, Cheepsunthorn P, Pavasant P, Sanchavanakit N (2008). Iron increases MMP-9 expression through activation of AP-1 via ERK/Akt pathway in human head and neck squamous carcinoma cells. Oral Oncol, 44, 587-94.   DOI   ScienceOn
20 Jawhari AU, Farthing MJ, Pignatelli M (1999). The E-cadherin/ epidermal growth factor receptor interaction: a hypothesis of reciprocal and reversible control of intercellular adhesion and cell proliferation. J Pathol, 187, 155-7.   DOI
21 Klagsbrun M, Soker S (1993). VEGF/VPF: the angiogenesis factor found? Curr Biol, 3, 699-702.   DOI   ScienceOn
22 Klein T, Bischoff R (2011). Physiology and pathophysiology of matrix metalloproteases. Amino Acids, 41, 271-90.   DOI
23 Kusukawa J, Sasaguri Y, Shima I, Kameyama T, Morimatsu M (1993). Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study. Am J Clin Pathol, 99, 18-23.   DOI
24 Kyzas PA, Stefanou D, Agnantis NJ (2004). Immunohistochemical expression of vascular endothelial growth factor correlates with positive surgical margins and recurrence in T1 and T2 squamous cell carcinoma (SCC) of the lower lip. Oral Oncol, 40, 941-7.   DOI   ScienceOn
25 Mareel M, Oliveira MJ, Madani I (2009). Cancer invasion and metastasis: interacting ecosystems. Virchows Arch, 454, 599-622.   DOI
26 Mook ORF, Frederiks WM, Noorden CV (2004). The role of gelatinases in colorectal metastasis. Biochim Biophys Acta, 1705, 69-89.
27 Mattijssen V, Peters HM, Schalkwijk L, et al (1993). E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. Int J Cancer, 55, 580-5.   DOI   ScienceOn
28 Nagafuchi A, Takeichi M (1989). Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. Cell Regul, 1, 37-44.
29 Mineta H, Miura K, Ogino T, et al (2000). Prognostic value of vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinomas. Br J Cancer, 83, 775-81.   DOI   ScienceOn
30 Miyajima Y, Nakano R, Morimatsu M (1995). Analysis of expression of matrix metalloproteinases-2 and -9 in hypopharyngeal squamous cell carcinoma by in situ hybridization. Ann Otol Rhinol Laryngol, 104, 678-84.   DOI
31 Navarro P, Gomez M, Pizarro A, et al (1991). A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis. J Cell Biol, 115, 517-33.   DOI   ScienceOn
32 Nijkamp MM, Span PN, Hoogsteen IJ, et al (2011). Expression of E-cadherin and vimentin correlates with metastasis formation in head and neck squamous cell carcinoma patients. Radiother Oncol, 99, 344-8.   DOI   ScienceOn
33 Nollet F, Kools P, van Roy F (2000). Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol, 299, 551-72.   DOI   ScienceOn
34 Page-McCaw A, Ewald AJ, Werb Z (2007). Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol, 8, 221-33.   DOI   ScienceOn
35 Rosado P, Lequerica-Fernandez P, Fernandez S, et al (2013). E-cadherin and $\beta$-catenin expression in well-differentiated and moderately-differentiated oral squamous cell carcinoma: relations with clinical variables. Br J Oral Maxillofac Surg, 51, 149-56.   DOI   ScienceOn
36 Sato F, Shimada Y, Watanabe G, et al (1999). Expression of vascular endothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in oesophageal cancer. Br J Cancer, 80, 1366-72.   DOI   ScienceOn
37 Peralta Soler A, Knudsen KA, Tecson-Miguel A, et al (1997). Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of the ovary distinguishes mucinous from serous and endometrioid tumors. Hum Pathol, 28, 734-9.   DOI   ScienceOn
38 Pilch BZ, Dorfman DM, Brodsky GL (1996). Goodman M. Pathology of laryngeal malignancies. In: Fried MP. ed. The larynx; A multidisciplinary Approach. 2nd ed. St Louis, CV Mosby, 425-36
39 Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A (2009). Distinct patterns of matrix metalloproteinase-2 and -9 expression in normal human cell lines. Oncol Rep, 21, 821-6.
40 Shima I, Sasaguri Y, Kusukawa J, et al (1992). Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study. Cancer, 70, 2747-53.   DOI
41 Shiozaki H, Tahara H, Oka H, et al (1991). Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol, 139, 17-23.
42 Stell PM (1990). Prognosis in laryngeal carcinoma: tumour factors. Clin Otolaryngol Allied Sci, 15, 69-81.   DOI
43 Takeichi M (1991). Cadherin cell adhesion receptors as a morphogenetic regulator. Science, 251, 1451-5.   DOI
44 Viros D, Camacho M, Zarraonandia I, et al (2013). Prognostic role of MMP-9 expression in head and neck carcinoma patients treated with radiotherapy or chemoradiotherapy. Oral Oncol, 49, 322-5.   DOI   ScienceOn
45 Zhao YG, Xiao AZ, Ni J, Man YG, Sang QX (2009). Expression of matrix metalloproteinase-26 in multiple human cancer tissues and smooth muscle cells. Ai Zheng, 28, 1168-75.
46 Talvensaari-Mattila A, Turpeenniemi-Hujanen T. (2005). Preoperative serum MMP-9 immunoreactive protein is a prognostic indicator for relapse-free survival in breast carcinoma. Cancer Lett, 217, 237-42.   DOI   ScienceOn
47 Wakisaka N, Wen QH, Yoshizaki T, et al (1999). Association of vascular endothelial growth factor expression with angiogenesis and lymph node metastasis in nasopharyngeal carcinoma. Laryngoscope, 109, 810-4.   DOI   ScienceOn
48 Wang Z, Chen Y, Li X, et al (2012). Expression of VEGF-C/ VEGFR-3 in human laryngeal squamous cell carcinomas and its significance for lymphatic metastasis. Asian Pac J Cancer Prev, 13, 27-31.   DOI   ScienceOn
49 Zhongliang W, Yao C, Rueixiang L (2002). Advanced in the researches for vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)-3. China J Cancer Prev Treat, 9, 454.
50 Bagutti C, Speight PM, Watt FM (1998). Comparison of integrin, cadherin, and catenin expression in squamous cell carcinomas of the oral cavity. J Pathol, 186, 8-16.   DOI
51 Acs G, Lawton TJ, Rebbeck TR, LiVolsi VA, Zhang PJ (2001). Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J ClinPathol, 115, 85-98.
52 Behrens J (1994). Cadherins as determinants of tissue morphology and suppressors of invasion. ActaAnat (Basel), 149, 165-9.   DOI
53 Andrews NA, Jones AS, Helliwell TR, Kinsella AR (1997). Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. Br J Cancer, 75, 1474-80.   DOI
54 Basset P, Bellocq JP, Wolf C, et al (1990). A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature, 348, 699-704.   DOI   ScienceOn
55 Behrens J, Mareel MM, Van Roy FM, Birchmeier W (1989). Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol, 108, 2435-47.   DOI   ScienceOn
56 Berx G, Van Roy F (2001). The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res, 3, 289-93.   DOI
57 Borgstrom P, Hillan KJ, Sriramarao P, Ferrara N (1996). Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res, 56, 4032-9.
58 Crissman JD, Zarbo RJ (1990). Squamous cell carcinoma of the upper aerodigestive tract: histologic parameters with prognostic value. In: Fee W.E. Jr, Goepfert H, Johans ME. et al (eds). Head and Neck Cancer, Vol. 2, Decker, Toronto.
59 Cavallaro U, Christofori G (2004). Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer, 4, 118-32.   DOI   ScienceOn
60 Eisma RJ, Spiro JD, Kreutzer DL (1999). Role of angiogenic factors: coexpression of interleukin-8 and vascular endothelial growth factor in patients with head and neck squamous carcinoma. Laryngoscope, 109, 687-93.   DOI   ScienceOn
61 Kugler A, Hemmerlein B, Thelen P, et al (1998). Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol, 160, 1914-8.   DOI   ScienceOn