前列腺癌ALK基因改变与蛋白表达

发布时间：2018-05-16 07:34

本文选题：前列腺癌 + ALK基因　；参考：《浙江大学》2014年硕士论文

【摘要】：[目的] 近来研究发现在非小细胞肺癌人群中存在间变性淋巴瘤激酶(ALK)基因重排,并可以应用克唑替尼对其进行靶向药物治疗。在乳腺癌、食管癌、大肠癌、肾癌等实体瘤中也发现了ALK基因改变,但在前列腺癌中还未见报道。本研究目的为检测前列腺癌细胞中是否存在ALK基因相关染色体异位,并探讨其临床意义。 [方法] (1)收集浙江大学附属第一医院病理科2008年至2012年前列腺癌标本192例,并将其制作成组织芯片； (2)运用FISH分离探针检测方法检测前列腺癌标本中EML4-ALK融合基因及ALK基因重排情况； (3)采用免疫组化Envision二步法检测192例中性福尔马林固定、石蜡包埋的前列腺癌标本中ALK基因蛋白表达； (4)统计学采用SPSS18.0软件进行卡方检验,P0.05作为显著性检验标准。 [结果] 在192例前列腺癌组织中FISH法有12例发生了ALK基因断裂缺失：发生率为6.25%。阳性细胞多为5’端缺失。前列腺癌中ALK基因重排与吸烟史、饮酒史、Gleason评分、年龄无显著相关(P0.05)。虽然各组间发生率未达到统计学差异,但ALK阳性率随年龄增加而增加(P=0.230)；饮酒组发生率高于不饮酒组(P=0.052)；吸烟组发生率高于不吸烟组(P=0.200)；PSA值10-20ng/ml组发生率高于20ng/ml以上组(P=0.164).未见EML4-ALK融合基因。ALK蛋白均定位表达于前列腺癌细胞胞核,免疫组化细胞着色浅,阳性细胞少,不能可靠应用于判断ALK是否阳性。 [结论] 该研究对192例前列腺癌标本进行了荧光原位杂和交免疫组化检测,发现前列腺癌中存在ALK基因重排,总阳性率为6.25%。同时未检测到前列腺癌中存在EML4-ALK融合基因。研究还发现阳性前列腺癌ALK蛋白定位表达于细胞核；ALK/5A4抗体免疫组化尚不能可靠应用于判断ALK阳性前列腺癌。此外研究进一步提示ALK基因重排与患者年龄、Gleason评分、吸烟、饮酒、TNM分期、PSA值没有相关性。
[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.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.25

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