本文選題：前列腺癌 + ALK基因�。� 參考：《浙江大學(xué)》2014年碩士論文

【摘要】：[目的] 近來研究發(fā)現(xiàn)在非小細(xì)胞肺癌人群中存在間變性淋巴瘤激酶(ALK)基因重排,并可以應(yīng)用克唑替尼對其進(jìn)行靶向藥物治療。在乳腺癌、食管癌、大腸癌、腎癌等實(shí)體瘤中也發(fā)現(xiàn)了ALK基因改變,但在前列腺癌中還未見報(bào)道。本研究目的為檢測前列腺癌細(xì)胞中是否存在ALK基因相關(guān)染色體異位,并探討其臨床意義。 [方法] (1)收集浙江大學(xué)附屬第一醫(yī)院病理科2008年至2012年前列腺癌標(biāo)本192例,并將其制作成組織芯片； (2)運(yùn)用FISH分離探針檢測方法檢測前列腺癌標(biāo)本中EML4-ALK融合基因及ALK基因重排情況； (3)采用免疫組化Envision二步法檢測192例中性福爾馬林固定、石蠟包埋的前列腺癌標(biāo)本中ALK基因蛋白表達(dá)； (4)統(tǒng)計(jì)學(xué)采用SPSS18.0軟件進(jìn)行卡方檢驗(yàn),P0.05作為顯著性檢驗(yàn)標(biāo)準(zhǔn)。 [結(jié)果] 在192例前列腺癌組織中FISH法有12例發(fā)生了ALK基因斷裂缺失：發(fā)生率為6.25%。陽性細(xì)胞多為5’端缺失。前列腺癌中ALK基因重排與吸煙史、飲酒史、Gleason評分、年齡無顯著相關(guān)(P0.05)。雖然各組間發(fā)生率未達(dá)到統(tǒng)計(jì)學(xué)差異,但ALK陽性率隨年齡增加而增加(P=0.230)；飲酒組發(fā)生率高于不飲酒組(P=0.052)；吸煙組發(fā)生率高于不吸煙組(P=0.200)；PSA值10-20ng/ml組發(fā)生率高于20ng/ml以上組(P=0.164).未見EML4-ALK融合基因。ALK蛋白均定位表達(dá)于前列腺癌細(xì)胞胞核,免疫組化細(xì)胞著色淺,陽性細(xì)胞少,不能可靠應(yīng)用于判斷ALK是否陽性。 [結(jié)論] 該研究對192例前列腺癌標(biāo)本進(jìn)行了熒光原位雜和交免疫組化檢測,發(fā)現(xiàn)前列腺癌中存在ALK基因重排,總陽性率為6.25%。同時(shí)未檢測到前列腺癌中存在EML4-ALK融合基因。研究還發(fā)現(xiàn)陽性前列腺癌ALK蛋白定位表達(dá)于細(xì)胞核；ALK/5A4抗體免疫組化尚不能可靠應(yīng)用于判斷ALK陽性前列腺癌。此外研究進(jìn)一步提示ALK基因重排與患者年齡、Gleason評分、吸煙、飲酒、TNM分期、PSA值沒有相關(guān)性。
[Abstract]:[purpose] Recent studies have found that anaplastic lymphoma kinase (ALK) gene rearrangements exist in non-small cell lung cancer (NSCLC) populations and can be targeted for drug therapy by cetatinib. ALK gene alterations have also been found in solid tumors such as breast cancer, esophageal cancer, colorectal cancer and renal cancer, but have not been reported in prostate cancer. The aim of this study was to detect the presence of chromosomal ectopic associated with ALK gene in prostate cancer cells and to explore its clinical significance. [methods] 1. 192 prostate cancer samples from Department of Pathology of the first affiliated Hospital of Zhejiang University from 2008 to 2012 were collected and made into tissue microarray. (2) EML4-ALK fusion gene and ALK gene rearrangement in prostate cancer samples were detected by FISH isolation probe method. (3) Immunohistochemical Envision two-step method was used to detect the expression of ALK gene in 192 prostate cancer specimens fixed with neutral formalin and embedded in paraffin. (4) SPSS18.0 software was used for chi-square test (P0.05). [results] ALK gene deletion was found in 12 out of 192 prostate cancer tissues by FISH: 6.25%. Most of the positive cells were 5 'terminal deletion. There was no significant correlation between ALK gene rearrangement and smoking history, drinking history and Gleason score in prostate cancer (P 0.05). Although the incidence of ALK did not reach statistical difference among the groups, the positive rate of ALK increased with the increase of age, the incidence of drinking group was higher than that of non-alcohol drinking group, and the incidence of smoking group was higher than that of non-smoking group. The incidence rate of 10-20ng/ml group was higher than that of 20ng/ml group. No EML4-ALK fusion gene. ALK protein was expressed in the nucleus of prostate cancer cells. The immunohistochemical staining was light and the positive cells were few. It could not be used to judge whether ALK was positive or not. [conclusion] In this study, ALK gene rearrangement was detected in 192 prostate cancer samples by fluorescence in situ hybridization and cross immunocytochemistry. The total positive rate was 6.25%. No EML4-ALK fusion gene was detected in prostate cancer. It was also found that the localization of ALK protein in the nucleus of prostate cancer was not reliable for the diagnosis of ALK positive prostate cancer by immunohistochemical staining of ALK / 5A4 antibody. Furthermore, it was suggested that there was no correlation between ALK gene rearrangement and Gleason score, smoking and alcohol consumption.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 季天海;李慧靈;蔣會(huì)勇;趙彤;余英豪;;ALCL染色體移位的間變性淋巴瘤激酶的表達(dá)及其與預(yù)后的關(guān)系[J];中國實(shí)驗(yàn)血液學(xué)雜志;2008年03期

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