口腔 및 口咽頭 扁平細胞癌腫에서 新生血管 生成과 Microsatellite의 變異 = Angiogenesis and microsatellite alterations in oral cavity and oropharyngeal squamous cell carcinoma

다국어 초록 (Multilingual Abstract)

Angiogenesis is an essential process in tumor growth and metastasis. A poor prognosis of oral cavity and oropharyngeal squamous cell carcinoma(SCC) is partly due to the local invasiveness and metastasis of the tumor. Angiogenic markers were significantly correlated with TNM stage, lymph node metastasis, and prognosis of cancers of various parts of body. Understanding the genetic alterations that occured in oral and oropharyngeal squamous cell carcinomas(SCCs) may help us understood their biology and behavior. However, little had been known about the correlation between angiogensis and genetic alterations in oral cavity and oropharyngeal squamous cell carcinoma.
The main objectives of this study are to examine the angiogenic markers(MMP-9, bFGF and microvessel density) and the microsatellite alterations(MSI and LOH) in oral cavity and oropharyngeal squamous cell carcinoma, and to investigate the correlation with various clinicopathological parameters.
From 40 cases of paraffin block specimens of oral cavity and oropharyngeal squamous cell carcinoma, the expressions of the MMP-9, bFGF and CD-34 were analyzed by using immunohistochemical method. And the MSI and LOH were analyzed by using microsatellite markers. MSI was examined at BAT25, BAT26, D2S123, D5S346 and D17S250 loci recommended in 1997 NIH international Workshop on Microsatellite Instabilities and RER phenotypes. LOH was examined at four p53 gene related loci including TP53, D17S796, D17S5, D17S513. Clinicopathological parameters, including T stage, lymph node metastasis, pathogic stage, histologic grade, recurrence rate and disease-free survival rate were compared with the incidence of MSI & LOH and expression of MMP-9, bFGF and CD-34.
MMP-9 and bFGF showed higher expression in squamous cell carcinoma than normal mucosa(p<0.05). Among the 28 cases with positive MMP-9 expression, 21 cases(75%) had increased expression of bFGF(p<0.05). And poor histologic differentiation has higher MVD, the margins of the tumor showed higher MVD than the portion of the tumor(p<0.05).
Each MSI & LOH were observed in 5 cases (2l%)and 14 cases(58%). All MSI occurred in well differentiated histological grade(p<0.05). The incidence of MSI was increased in the cases with low pathologic stage. And the incidence of LOH was increased in the presence of nodal metastasis, in the cases with poorly differentiated histologic grade and in the cases with high MMP-9 expression. MSI & LOH had inverse relationship.
These results may suggest that microsatellite alterations(MSI and LOH) have an important role in carcinogenesis and angiogenesis of oral cavity and oropharyngeal squamous cell carcinoma. Also, it is suggested that angiogenic markers and microsatellite alterations(MSI & LOH) may be useful prognostic indicators of oral cavity and oropharyngeal squamous cell carcinoma.

목차 (Table of Contents)

• 목차
• Ⅰ. 서론 = 1
• Ⅱ. 대상 및 방법 = 3
• 1. 대상 = 3
• 2. 방법 = 3
• Ⅲ. 결과 = 9
• 1. 임상 및 조직병리학적 소견 = 9
• 2. 면역조직화학적 발현 양상 = 9
• 3. 분자생물학적 검사결과 = 15
• Ⅳ. 고찰 = 22
• Ⅴ. 결론 = 28
• 참고문헌 = 30
• ABSTRACT = 37