臺灣博碩士論文加值系統

人類的原發性乳癌之癌化過程被認為是經由漸進性的演變，由增生到原位癌最後變成侵犯型乳癌，在本實驗中乳癌組織的顯微剝離技術是被使用來檢查微衛星小體(microsatellite)的改變，包括微衛星小體的不穩定性(microsatellite instability;MI)及異形合子的喪失(loss of heterozygosity;LOH)於腺管內原位癌(intraductal carcinomain situ;DCIS)及侵犯性腺管癌(invasive ducatl carcinoma;IDC)的情形，經由比較同一病例腫瘤與正常乳房組織的不同，以四個位於第十一對染色體的微衛星小體標誌 (microsatellite markers)是被使用來檢測共30例檢體包括10例DCIS及20例IDC'MI及LOH的發生率是經由比較由蠟塊包埋的檢體藉聚合晦連鎖反應 (PCR)放大的序列，分析結果顯示有37.9%(11/29)乳癌組織為MI(+)，而在DCIS中為20%(2/10)，IDC中為47.4%(9/19)，可看出MI在IDC的發生率明顯高於在 DCIS的發生率，此外 MI(+)與腫瘤大小(p=0.004)、分期(p<0.001)及黃體激素受體(PR;p<0.01)等臨床病理學特徵的關係具有統計學上的意義，但在年齡、淋巴結侵犯、惡性度分級、動情激素受體(ER)及p53等因子並無有意義的相關性，然而結果亦顯示MI(+)乳癌組織其PR及P53都有低表現的趨勢。
在 LOH的檢測中，分析結果顯示在 D11S905有 10.3%、D11S912有11%、D11S934有17.2%但在D11S935並未有LOH的出現，因此可知在介於D11S912及D11S934的llq2.3-24區域上有27%出現LOH現象且明顯位於IDC上。
根據結果可歸納出乳癌所招致的複製錯誤的表現型是與其晚期有相關性，且複製錯誤的表現型與侵犯性腺管癌的侵襲性有相關性。同時結果也隱含著錯誤配對修補的缺損能改變黃體激素受體的表現。

Human primary breast carcinoma is thought to develop through progressive change from hyperplasia to in situ carcinoma and eventually to invasive cancer. In this study, tissue microdissection was be used to examine the microsatellite alteration, including microsatellite instability (MI) and loss ofheterzygosity (LOH), in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), as compared to normal breast tissue from same patients. Four microsatellite markers were used to investigate 30 cases, including ten DCIS and twenty IDC. The incidence of MI and LOH was perfonnanced by comparing PCR-amplified sequence from paraffin-embedded samples. This analysis showed that 37.9% (11/29) of breast cancers exhibit MI(+). Ml(+) was detected in 20% (2/10) of DCIS and in 47.4% (9/19) in IDC. The frequency of MI in IDC is higher than that in DCIS. In addition, MI significantly correlated with clinicopathological features, including tumor size (p=0.004), stage (p<0.001) and progesterone receptor (PR; p<0.01), but no significant correlation with age, lymph node involvement, grade, estrogen receptor (ER) and p53. The results also showed a trend of low expressing PR and p53 observed associating with MI.
In the detection of LOH, the analysis showed that 10.3% in D11S905, 11% in D11S912, 17.2% in D11S934 and zero in D11S935. The results showed that 27% of the tumors exhibited LOH at llp23.3-24 region between loci D11S934 and D11S912 with IDC predominantly.
Our results suggest that breast carcinomas acquire the replication error (RER) phenotype in the relatively late stages, and that the RER phenotype is associated with aggressiveness of IDC. The result also implicated mismatch repair failure can alter the expression of PR.