| Abstract: | 乳腺癌為全世界女性發生率最高的癌症，每年有一百一十五萬新增病例，佔全世界每年癌症人數一千一百萬的百分之十。近年來，台灣每年也有將近六千名新增的乳腺癌病例，且發病年齡有年輕化之趨勢，好發年齡高峰期在四十五至五十五歲之間，與西方歐美國家相較年輕十歲。由於乳腺癌須依賴乳房超音波、乳房磁振掃描、傳統的病理組織學，作為篩檢、診斷及治療的預後相關因子外，尚需輔以生物腫瘤標記作為參考。基於以上所述特性，針對台灣婦女乳腺癌的研究，成為一個重要的課題。
近幾年的文獻提到乳腺癌表現因子除了雌激素接受體(ER)、黃體激素接受體(PR)及腫瘤蛋白Her-2/neu和預後有相關以外，乳腺癌發生機轉也與生物發育中佔極重要角色的Notch signal pathway有關，其中Notch family接受體Notch1和與其結合之受質Jagged1、Delta之表現和腫瘤蛋白HER-2/neu之表現有關聯，因此我們想更進一步分析Notch1、Jagged1、Delta三者之相對表現差異。本研究利用組織微陣列工具，針對兩類型乳腺癌來建立組織晶片。而此兩類型區分，以病理報告中的乳腺癌表現因子ER/PR及腫瘤蛋白HER-2/neu陽性或陰性來區分，分為ER/PR陰性和HER-2/neu陽性，以及ER/PR陽性而HER-2/neu陰性兩大類，再以取出癌症組織建立組織晶片。利用所建立乳腺癌組織晶片，以Notch1、Jagged1、Delta之抗體進行免疫組織化學染色，所得之結果利用卡方檢定及Spearman等級相關係數檢定，統計分析。
其結果呈現在59案例中，HER-2/neu的表現與組織惡性度有正相關性。而Notch1的表現量和組織惡性度呈現負相關性。Jagged1在乳腺癌組織的表現和Notch1相似。但Delta表現量則與Jagged1的表現呈現負相關。最後，Jagged1的表現與組織惡性度呈現負相關性。但是在HER-2/neu陰性條件下，Jagged1的表現與組織惡性度呈現正相關性。
關鍵字：雌激素接受體、黃體激素接受體、腫瘤蛋白HER-2/neu、卡方檢定、組織微陣列、組織惡性度
Breast cancer has the highest incidence in all the malignancy in the world. Around 1.15 million new cases of breast cancer are found every year, which are accounted for ten percent of the 11 million people newly-diagnosed with cancer. In recent years, there are near six thousand new cases of breast cancer occurring in Taiwan, and their age have a younger tendency. The peak age of breast cancer in Taiwan is around 45-55 years old, which is 10 years younger than that in the western countries. For screening, diagnosis and treatment of breast cancer, breast ultrasound, magnetic resonance imaging, and traditional histopathology are still the gold standard. Tumor markers such as estrogen receptor, progesterone receptor and oncoprotein Her-2/neu are also known as a guidance for prognosis. Therefore, the specific study of breast cancer in Taiwan women becomes an important issue.
Recent studies suggest that breast cancer biomarkers are estrogen receptor (ER), progesterone receptor (PR) and oncogene protein Her-2/neu, and they are related to prognosis. Notch signal pathway, which plays important role in biological development, is also related to the pathogenetic mechanism of breast cancer. One of Notch family receptors, Notch1, and its ligands Jagged1 and Delta, the expression of are associated with tumor-related protein Her-2/neu expression. Therefore, we would like to further analyze the differential expression between Notch1, Jagged1 and Delta in different sets of breast tumors. In this study, we use tissue microarray as a tool to establish tissue microarrays for two different types of breast cancer. In this study, breast cancer is classified into two groups based on pathologic reports of ER, PR and Her-2/neu expression, positive and/or negative. The two groups are ER/PR negative and Her-2/neu positive, and ER/PR positive and Her-2/neu negative. Then we established tissue microarrays, which were taken from breast cancer tissue cores. Notch1, Jagged1, and Delta protein expression were evaluated by immunohistochemistry in tissue microarrays of breast caner. The association between the expression patterns of these proteins and biomarkers of breast cancer were analyzed by χ2 test and Spearman’s rank correction test.
In the total 59 cases, expression of HER-2/neu and the tumor grading of invasive breast cancer shows positive correlation. The expression of Notch1 and tumor grade of invasive breast cancer presents negative correlation. The expression of Jagged1 in invasive breast cancer is similar to that of Notch1. Delta expression strength reveals negative correlation to the expression of Jagged1. Finally, expression of Jagged1 and tumor grade of invasive breast cancer presents negative correlation. But under negative condition of HER-2/neu, the tumor grading of invasive breast cancer shows positive correlation. |
