Browse > Article

Correlations of Oral Tongue Cancer Invasion with Matrix Metalloproteinases(MMPs) and Vascular Endothelial Growth Factor(VEGF) Expression  

Kim Se-Heon (Department of Otorhinolaryngology, Yonsei University College of Medicine)
Cho Nam-Hoon (Department of Pathology, Yonsei University College of Medicine)
Lim Jae-Yul (Department of Otorhinolaryngology, Yonsei University College of Medicine)
Kim Ji-Hoon (Department of Otorhinolaryngology, Yonsei University College of Medicine)
Kim Jeong-Hong (Department of Otorhinolaryngology, Yonsei University College of Medicine)
Chang Jung-Hyun (Department of Otorhinolaryngology, Yonsei University College of Medicine)
Choi Eun-Chang (Department of Otorhinolaryngology, Yonsei University College of Medicine)
Publication Information
Korean Journal of Head & Neck Oncology / v.21, no.1, 2005 , pp. 3-9 More about this Journal
Abstract
Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.
Keywords
Oral tongue carcinoma; Tumor thickness; VEGF; MMPs;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Spiro RH, Huvos AG, Wong GY, Spiro JD, Gnecco CA, Strong EW : Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg. 1986;152 (4):345-350   DOI   ScienceOn
2 Shin CH, Ozawa S, Ando N, Ueda M, Kitajima M : Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res. 2000;6 (3):1161-1168
3 Folkman J, Watson K, Ingber D, Hanahan D : Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature. 1989;339(6219):58-61   DOI   ScienceOn
4 Folkman J. Growth and metastasis of tumor in organ cultures. Cancer. 1963;16:453-467   DOI   PUBMED   ScienceOn
5 Ryohei Katoh. Expression of Vasculaar Endothelial Growth Factor (VEGF) in Human Thyroid Neoplasm. Human pathology. 1999;30(8):891-897   DOI   PUBMED   ScienceOn
6 Ho CM, Lam KH, Wei WI, Lau SK, Lam LK : Occult lymph node metastasis in small oral tongue cancers. Head & Neck. 1992;14(5):359-363   DOI   ScienceOn
7 Shindoh M, Higashino F, Kaya M, Yasuda M, Funaoka K, Hanzawa M, Hida K, Kohgo T, Amemiya A, Yoshida K, Fujinaga K : Correlated expression of matrix metalloproteinases and ets family transcription factor E1A-F in invasive oral squamous-cell-carcinoma-derived cell lines. Am J Pathol. 1996;148 (3):693-700
8 Plate KH, Breier G, Weich HA, Risau W : Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature. 1992;359(6398):845-848   DOI   ScienceOn
9 Tokio Osaki, Tsuyoshi Kimura, Yukihiro Tatemoto, Tetsuya Yamamoto, Kazunori Yoneda : Risk Factors of Metastasis in Oral squmous Cell Carcinomas. Oncology. 2000;58:137-143   DOI   ScienceOn
10 Folkman J : Endothelial cells and angiogenic growth factors in cancer growth and metastasis. Introduction. Cancer Metastasis Rev. 1990;9(3):171-174   DOI   ScienceOn
11 Stetler-Stevenson WG, Liotta LA, Kleiner DE Jr : Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J. 1993;7(15):1434-1441
12 Fukano H, Matsuura H, Hasegawa Y, Nakamura S : Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head & Neck. 1997;19(3):205-210   DOI   ScienceOn
13 Smith BD, Smith GL, Carter D, Sasaki CT, Haffty BG : Prognostic significance of vascular endothelial growth factor protein levels in oral and oropharyngeal squamous cell carcinoma. J Clin Oncol. 2000;18(10):2046-2056
14 Weidner N, Semple JP, Welch WR, Folkman J : Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991:324 (1):1-8   DOI   ScienceOn
15 Kurahara S, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A, Takeuchi H, Shirasuna K : Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head & Neck. 1999;21(7):627-638   DOI   ScienceOn
16 Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW : The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991;5(12):1806-1814   DOI   ScienceOn
17 Po Wing Yuen A, Lam KY, Lam LK, Ho CM, Wong A, Chow TL, Yuen WF, Wei WI : Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck. 2002:24(6):513-520   DOI   ScienceOn
18 Manabu Ohta, Hiroyuki Konno, Tatwuo Tanaka, et al. The significance of circulating vascular endothelial growth factor (VEGF) protein in gastric cancer. Cancer Letters. 2003;31(2):215-225   DOI   ScienceOn
19 Michelel R, Susan LJ, Prudence AES, Stephen F, Kenneth S, Russell L : Expression of the angiogenic factor. Vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor ${\beta}$-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res. 1997;57:963-969
20 Asakage T, Yokose T, Mukai K, Tsugane S, Tsubono Y, Asai M, Ebihara S : Tumor thickness predicts cervical metastasis in patients with stage I/II carcinoma of the tongue. Cancer. 1998;82 (8):1443-1448   DOI   PUBMED   ScienceOn
21 Tatsuya F, Yuji T, Suminori A, Tsutomu M, Yutaka H, Kazutaka M : Expression of thymidine phosphorylase and vascular endothelial cell growth factor in human head and neck squamous cell carcinoma and their different characteristics. Cancer. 1999;85:960-969   DOI   PUBMED   ScienceOn
22 Shintani S, Matsuura H, Hasegawa Y, Nakayama B, Fujimoto Y : The relationship of shape of tumor invasion to depth of invasion and cervical lymph node metastasis in squamous cell carcinoma of the tongue. Oncology. 1997;54 (6):463-467   DOI   ScienceOn
23 O-charoenrat P, Rhys-Evans P, Eccles SA : Expression of vascular endothelial growth factor family members in head and neck squamous cell carcinoma correlates with lymph node metastasis. Cancer. 2001;92 (3):556-568   DOI   PUBMED   ScienceOn
24 O'Brien CJ, Lauer CS, Fredricks S, Clifford AR, McNeil EB, Bagia JS, Koulmandas C : Tumor thickness influences prognosis of T1 and T2 oral cavity cancer-but what thickness? Head Neck. 2003;25(11):937-945   DOI   ScienceOn