臺灣博碩士論文加值系統

HER-2/neu proto-oncogene的放大(amplification)或HER-2/neu oncoprotein的過度表現(over-expression)，被認為是影響乳癌患者治療反應及預後的重要因素，同時也是提供是否使用Herceptin( Trastuzumab )治療的依據。以往的研究統計顯示，一般乳癌患者的HER-2/neu oncoprotein過度表現的比率約佔10%－40%，家族性乳癌的HER-2/neu oncoprotein的表現率，是否比一般或非家族性的表現率高，是值得探討的主題。本文蒐集自一九九○到一九九九年之間，56例家族性乳癌及111例非家族性乳癌，使用組織化學免疫染色來比較HER-2/neu oncoprotein過度表現的差異，並與腫瘤的組織型態、分級及分期作相關性的分析，結果顯示家族性乳癌整體的HER-2/neu oncoprotein表現陽性率比非家族性乳癌高，分別為50%及36.9%，兩者在統計上沒有意義(P=0.1068)，但如果針對浸潤性腺管癌(infiltrating ductal carcinoma)作比較，分別為52.3%和33.7%，兩者則有差異(P=0.0429)。在非家族性及整體的乳癌病例，HER-2/neu oncoprotein表現陽性率和侵襲性腺管癌組織形態的分級(histological grade)與淋巴結的轉移相關，而組織形態中和細胞分裂(mitotic counts)及細胞核的多形性(nuclear pleomorphism)有關，但與小管腔的形成(tubule formation)不相關。3例Paget''s disease的HER-2/neu oncoprotein的表現都呈陽性，而12例黏液腺癌(mucinous carcinoma)，1例髓樣癌(medullary carcinoma)及1例化生癌(metaplastic carcinoma)則都呈陰性。腺管內癌(intraductal carcinoma)的HER-2/neu oncoprotein表現陽性率在兩組都很高，分別為57.1%和73.3%，兩者在統計上沒有差異(P=0.4716)，以往的研究報告發現，粉刺型的腺管內癌的HER-2/neu oncoprotein 的表現大多是陽性，所以如果粉刺型的腺管內癌的病例所佔的比率較多，便會造成整體的HER-2/neu oncoprotein表現陽性率較高。在1例伴有浸潤性腺管癌及腺管內癌的腫瘤，出現浸潤性癌細胞呈陰性的HER-2/neu oncoprotein染色，而腺管內癌細胞呈現較強的非均質染色，顯示部份腺管內癌在進展到侵襲性腺管癌時，其HER-2/neu oncoprotein的表現可能會減少，這可推測HER-2/neu oncoprotein 的過度表現在腺管內癌，Paget''s disease和侵襲性乳癌可能具有不同的意義，所以在統計乳癌的HER-2/neu oncoprotein過度表現率時，應依腫瘤病理組織形態類別分開作統計及比較。

The HER-2/neu proto-oncogene amplification or oncoprotein over-expression is an important prognostic factor and a predictive factor for resistance to endocrine therapy and adjuvant chemotherapy in breast cancers. Moreover, it is an entry criterion in the assessment of patients for whom Herceptin (Trastuzumab) treatment is considered. The over-expression rate of HER-2/neu oncoprotein has been identified in 10% to 40% of human breast cancers. It is worthwhile to evaluate whether the over-expression is more frequent in familial breast cancers. Fifty-six familial and 111 non-familial breast cancers between 1990 and 1999 were included in this study to assess the over-expression of HER-2/neu oncoprotein immunohistochemically and the correlation with the histological type, grade and stage of breast carcinoma. The over-expression rate is higher in the familial breast cancers (50%) compared with non-familial breast cancers (36.9%), which did not prove to be statistically significant (P=0.1068). When the infiltrating duct carcinomas of both groups are compared, it is statistically significant (52.3% vs. 33.7%, P=0.0429). The over-expression correlated with node status and histological grade of infiltrating duct carcinomas in non-familial and overall breast cancers. It correlated with nuclear pleomorphism and mitotic counts, but not tubule formation or tumor size. All the 3 cases of Paget''s disease revealed over-expression, whereas all the 12 cases of mucinous carcinomas, a case of metaplastic carcinoma and a case of medullary carcinoma are negative. The over-expression rate was higher both in familial and non- familial intraductal carcinomas (57.1% vs. 73.3%, P=0.4716). No statistical difference is identified between the 2 subsets. The over-expression was reported mainly in comedo type of intraductal carcinoma with large, pleomorphic nuclei. A case of infiltrating duct carcinoma combined with intraductal carcinoma revealed heterogene- ous staining in the component of ductal carcinoma in situ, while the invasive component did not. It suggests that overexpression decreases within individual tumors as they evolve from in situ to invasive lesions. The HER-2/neu may imply a different role in the intraductal carcinoma, Paget''s disease and invasive duct carcinoma. It is appropriate to evaluate the rate of HER-2/neu over-expression according to the histological type of breast cancers.

1. 摘要…………………………………………3
2. 致謝…………………………………………5
3. 前言…………………………………………7
4. 文獻回顧……………………………………9
5. 材料與方法…………………………………12
6. 附表(一) …………………………………….15
7. 附圖…………………………………………16
8. 結果…………………………………………19
9. 附表(三) ……………………………………21
10. 討論…………………………………………29
11. 結論…………………………………………31
12. 參考文獻……………………………………32

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