胃癌之黏多醣、血管新生及黏著因子的組織化學和免疫組織化學研究

The Histochemical and Immunohistochemical Study of Mucopolysaccharide, Angiogenesis and Adhesion Molecule in Gastric cancer

孫家棟(Chia-Tung Shun)

指導教授 ： 饒宇東

國立臺灣大學/醫學院/病理學研究所/博士(2007年)

https://doi.org/10.6342/NTU.2007.00523

摘要

雖然藥物治療和衛生統計的進展降低了癌症的死亡率，但胃癌始終佔有癌症罹患和死亡的高位，甚至在遠東地區如：日本佔有第一位死亡率。所以，提高診斷率和找出相關的預後的評估因子實為很重要的課題。本論文完全利用傳統的組織化學染色和簡單的免疫組織化學染色來進行研究及評估。第一部份，我們發現胃癌的危險因子，尤其是Lauren氏腸型分類中的慢性萎縮性胃炎和具有硫性黏液的第Ⅲ型或ⅡB型的腸型化生與胃癌的發生有極密切的關係，兩者是評估胃癌發生的高危險因子；第二部份，我們探討是胃癌血管新生和抑癌基因蛋白質p53的關連性，結果我們發現血管新生因子三環類氧合酶-2在進行性胃癌或賁門癌有相當密切的關連性，但與幽門桿菌的存在與否沒有統計上的意義存在；第三部份，我們探討的是胃癌生成中細胞激素所扮演的角色，我們主要探討的是巨噬細胞遷徙抑制因子的角色，我們發現此因子在統計上與抑癌基因p53的相關性不大，但卻在腫瘤的進行和血管新生上扮演有重要的角色；最後探討的是黏著因子和胃癌生成關係，結論發現上皮性黏著因子的喪失與胃癌的生成、轉移、甚至胃癌病人的存活率都有密切的相關性存在；此外，我們亦發現不正常黏著因子複合體(Cadherin-Catenin Complex)的呈現在早期胃癌的癌發生上亦佔有一角色，更加發現這複合體的功能異常與淋巴結的轉移亦存有相當密切的關係。結論顯示胃癌是多因子的生成理論，將這些相關因子串聯起來，將是提升治療和預測胃癌病人預後的新思維。

關鍵字

胃癌 ； 黏多醣 ； p53蛋白 ； 三環類氧合酶-2 ； 巨噬細胞遷徙抑制因子 ； 上皮性黏著因子 ； 黏著因子複合體

並列摘要

Despite its decline in incidence of cancer death, gastric cancer remains the second most frequent cancer in the world and even the leading cause of death in the Far East, such as Japan. So how to improve the diagnosis and find the prognosis associated factors become an important issue in this field. In this research, we made use of classical histochemical methods and simple immunohistochemical methods. In the first part, we found the early risk factor of gastric cancer especially the Lauren’s intestinal type: chronic atrophic gastritis and the typeⅢ/ⅡB intestinal metaplasia with sulfur mucopolysaccharide change which also have correlated with the mutation of oncosuppressor gene p53. The second part of this paper, we discussed the factors associated with angiogenesis and their relationship with the oncosuppressor protein p53. We find that the close related angiogenetic factor, cyclooxygenase-2 (Cox-2), has high association with the p53 in gastric cancer, especially in advanced gastric cancer and cardiac type but not associated with Helicobacter pylori statistically. The 3rd part in this research, we discussed the role of cytokine in the gastric carcinogenesis. We focused on the macrophage migration inhibitor factor (MIF). It revealed that the macrophage migration inhibitor factor had no statistically significance with p53 but it played an important role in gastric cancer progression and neovasculization (angiogenesis with carcinogenesis). Finally we discussed the change of adhesion molecular in the gastric carcinogenesis. It showed the loss of E-cadherin in gastric cancer had close relationship with the gastric cancer formation, metastasis and even the survival rate of the patients. Furthermore, the abnormal expression of E-cadherin–catenin complex occurred frequency in gastric carcinogenesis especially at the early stage of diffuse type gastric cancer. In addition, lymph node metastasis had close relation to the dysfunction of this system. In conclusion, gastric carcinogenesis was multifactorial and how to link those factors will give us a new thinking process in treating and predicting the outcome of those types of patients.

並列關鍵字

gastric cancer (GC) ； mucopolysaccharide ； P-53 ； cyclooxygenase-2 (Cox-2) ； macrophage migration inhibitor factor (MIF) ； E-cadherin ； cadherin-catenin complex

參考文獻

mucosa with intestinal metaplasia. Eur J Gastroenterol

with enhanced angiogenesis and advanced stage in gastric

2.Houghton J, and Wang TC. Tumors of the stomach. In

Sleisenger and Fordtran’s Gastrointestinal and Liver

Saunder Elsevier, Philaddphia, PA. 2006;1139-1170