【摘要】：背景:乳腺癌是女性最常見的惡性腫瘤,嚴(yán)重危害著女性的健康和生命,新型特異性標(biāo)志物的檢測在乳腺癌早期診斷及治療中發(fā)揮著重要作用。目前研究表明,TYK2(Tyrosine Kinase 2,酪氨酸激酶2)高表達(dá)可促進(jìn)腫瘤細(xì)胞的增殖及侵襲能力,但其在乳腺癌發(fā)生與演變過程中的作用有細(xì)胞和組織特異性,有待深入研究。P53作為熟知的抑癌基因,在細(xì)胞周期、細(xì)胞凋亡等過程中起重要調(diào)控功能,而P53在腫瘤中發(fā)生突變則促進(jìn)腫瘤的惡性發(fā)展。有研究表明,在肺癌細(xì)胞中誘導(dǎo)野生型P53表達(dá)可通過一種E3泛素連接酶SIAH2(seven-in-absentia-2)下調(diào)TYK2的表達(dá),進(jìn)而影響下游信號(hào)通路,這提示P53與TYK2之間存在調(diào)控現(xiàn)象。而TYK2、P53在乳腺癌中表達(dá)的相關(guān)性鮮有研究報(bào)道。目的:檢測TYK2和P53在臨床乳腺組織標(biāo)本中的表達(dá)情況,分析其與患者年齡、絕經(jīng)狀態(tài)、淋巴結(jié)轉(zhuǎn)移等病理特征間的關(guān)系及意義;探討二者在乳腺癌中的表達(dá)是否相關(guān),并闡明潛在的臨床指導(dǎo)意義。方法:收集大連醫(yī)科大學(xué)附屬第二醫(yī)院2013年09月-2016年09月期間行手術(shù)切除的乳腺病理組織標(biāo)本152例,其中乳腺癌102例、纖維腺瘤30例、癌旁組織20例。采用免疫組織化學(xué)染色方法對TYK2和P53在三種不同乳腺組織中的表達(dá)情況進(jìn)行檢測,分析與臨床病理特征之間的關(guān)系,探討二者在乳腺癌中表達(dá)的相關(guān)性。結(jié)果:(1)TYK2在乳腺癌組織中高表達(dá),陽性表達(dá)率為57.84%(59/102),高于乳腺纖維腺瘤組織(6.67%)及癌旁組織(0.00%);P53在乳腺癌組織中高表達(dá),陽性表達(dá)率為40.20%(41/102),高于乳腺纖維腺瘤組織(3.33%)及癌旁組織(0.00%)。(2)TYK2在乳腺癌組織中的表達(dá)與腫瘤大小、臨床分期、ER、PR及Ki-67狀態(tài)相關(guān)(p0.05),而與患者年齡、絕經(jīng)狀態(tài)、淋巴結(jié)轉(zhuǎn)移、有無脈管或神經(jīng)侵犯、HER-2狀態(tài)無顯著相關(guān)性(p0.05)。P53在乳腺癌中的表達(dá)與淋巴結(jié)轉(zhuǎn)移、ER、PR及Ki-67狀態(tài)(p0.05)相關(guān),而與患者年齡、絕經(jīng)狀態(tài)、腫瘤大小、有無脈管或神經(jīng)侵犯、臨床分期、HER-2狀態(tài)無明顯相關(guān)性(p0.05)。TYK2在乳腺癌各分子分型中的陽性表達(dá)率分別為42.31%(Luminal A型)、54.55(Luminal B型)、61.90%(HER-2過表達(dá)型)和77.27%(三陰性);P53的陽性表達(dá)率分別為19.23%(Luminal A型)、33.33%(Luminal B型)、42.86%(HER-2過表達(dá)型)和72.73%(三陰性);P53在三陰性乳腺癌中表達(dá)水平較高,有統(tǒng)計(jì)學(xué)差異(X2=15.148,p=0.002)。(3)經(jīng)Spearman相關(guān)分析,TYK2和P53在乳腺癌總體樣本中的表達(dá)具有正相關(guān)性(r=0.560,p=0.000)。結(jié)論:(1)TYK2和P53在乳腺癌中的表達(dá)高于乳腺纖維腺瘤組織及癌旁組織;P53在三陰性乳腺癌中的陽性表達(dá)率高于其他分子分型。(2)乳腺癌中TYK2的表達(dá)與腫瘤大小、臨床分期、ER、PR及Ki-67狀態(tài)相關(guān);P53的表達(dá)與淋巴結(jié)轉(zhuǎn)移、ER、PR及Ki-67狀態(tài)相關(guān)。(3)TYK2和P53在乳腺癌中的表達(dá)有正相關(guān)性;聯(lián)合檢測二者的表達(dá)可為臨床乳腺癌的診斷、治療及預(yù)后評估等提供更準(zhǔn)確的參考。
[Abstract]:Background: breast cancer is the most common malignant tumor in women, which seriously endangers the health and life of women. The detection of new specific markers plays an important role in the early diagnosis and treatment of breast cancer. Recent studies have shown that the high expression of TYK2 (Tyrosine Kinase 2 and tyrosine kinase 2) can promote the proliferation and invasion of tumor cells, but its role in the occurrence and evolution of breast cancer is cell and tissue specific. P53, as a well-known tumor suppressor gene, plays an important role in cell cycle, apoptosis and other processes, while p53 mutation in tumors promotes the malignant development of tumors. Some studies have shown that inducing the expression of wild type p53 in lung cancer cells can down-regulate the expression of TYK2 through an E3 ubiquitin ligase SIAH2 (seven-in-absentia-2), which may affect the downstream signal pathway, which suggests that there is a regulatory phenomenon between p53 and TYK2. However, the correlation of TYK2,P53 expression in breast cancer is rarely reported. Objective: to detect the expression of TYK2 and p53 in clinical breast tissues and analyze their relationship with pathological features such as age, menopausal status, lymph node metastasis and so on. To explore the relationship between the expression of the two in breast cancer and to elucidate the potential clinical significance. Methods: 152 cases of breast pathological tissue were collected from September 2013 to September 2016 in the second affiliated Hospital of Dalian Medical University, including 102 cases of breast cancer, 30 cases of fibroadenoma and 20 cases of paracancerous tissue. The expression of TYK2 and p53 in three different breast tissues was detected by immunohistochemical staining, and the relationship between the expression of p53 and clinicopathological features was analyzed, and the correlation between the expression of p53 and p53 in breast cancer was discussed. Results: (1) the positive expression rate of TYK2 in breast cancer was 57.84% (59 鈮，

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