PTEN和P53及P16在不同形态大肠侧向发育型肿瘤中的表达
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摘要
[目的]观察抑癌基因PTEN、P53、P16蛋白在大肠侧向发育型肿瘤(LST)及其三分型中表达变化,探讨3者在LST发展进程中作用。[方法]选取经内镜下ESD治疗切除的90例大肠组织为LST组,另选取同时期80例经内镜下ESD治疗切除的大肠隆起型腺瘤(PA)大肠组织为PA组,以及70例结肠镜检查为全结肠未见器质性病变的患者正常大肠组织为对照组。在内镜下将90例LST分为颗粒均一型(LST-G-H)27例、结节混合型(LST-G-M)25例及非颗粒型(LST-NG)38例,并比较其临床资料;采用免疫组织化学法(SP法)检测PTEN、P53、P16蛋白水平。[结果]LST及其三亚型患者病变直径均明显大于PA患者(P<0.05)。LST病变多分布于直肠,PA病变多位于远端结肠,2者比较差异有统计学意义(P<0.05)。LST患者中组织学类型所占比例依次为绒毛状腺瘤、管状绒毛状腺瘤、管状腺瘤、锯齿状腺瘤;PA病变中管状腺瘤所占比例最高,无锯齿状腺瘤;其中,LST-G-H、LST-G-M中以绒毛状腺瘤为主,LST-NG中管状绒毛状腺瘤所占比例最高。LST癌变率显著高于PA(P<0.05)。PTEN、P16蛋白表达LST患者最低、PA患者次之、对照组最高;P53蛋白表达LST患者最高、PA患者次之、对照组最低。LST-NG患者PTEN蛋白表达显著低于LST-G-H组、LST-G-M组(P<0.05),P53、P16蛋白阳性率明显高于LST-G-H组、LST-G-M组(P<0.05)。[结论]PTEN、P16在LST患者大肠组织中表达下调,P53表达上调,可能参与LST特别是LST-NG发生发展。
[Objective]To observe the expression of PTEN, P53 and P16 proteins in laterally spreading tumor(LST) and their three subtypes, and to explore their roles in the development of LST. [Methods]90 cases of colorectal tissues resected by endoscopic submucosal dissection were selected as group LST, another 80 cases of protruded-type colorectal adenoma(PA) resected by ESD at the same time were selected as PA group, and 70 cases of normal colorectal tissues of patients without organic lesions in the whole colon examined by colonoscopy as control group. 90 cases of LST were divided into 3 groups, 27 cases of granular homogeneous type(LST-G-H), 25 cases of nodular mixed type(LST-G-M) and 38 cases of non-granular type(LST-NG) and their clinical data were compared; the levels of PTEN, P53 and P16 were detected by immunohistochemical method(SP). [Results]The lesion diameter of LST and three subtypes patients was significantly larger than that of PA patients(P<0.05). LST lesions are mostly distributed in the rectum, PA lesions mostly located in distal colon and the difference between them is significant(P<0.05). The proportion of histological types in LST patients was villous adenoma, tubular villous adenoma, tubular adenoma and serrated adenoma in turn; tubular adenomas accounted for the highest proportion of PA lesions, and there was no serrated adenoma; villous adenoma was the predominant lesion in LST-G-H and LST-G-M, tubular villous adenoma accounts for the highest proportion in LST-NG. The canceration rate of LST was significantly higher than that of PA(P<0.05). The expression of PTEN and P16 protein in LST patients was the lowest, followed by PA patients and the highest in control group; the expression of P53 protein was highest in LST patients, followed by PA patients and the lowest in control group. The expression of PTEN protein in LST-NG patients was significantly lower than that in LST-G-H and LST-G-M groups(P<0.05), the positive rates of P53 and P16 protein were significantly higher than those of LST-G-H and LST-G-M groups(P<0.05). [Conclusion]The expression of PTEN and P16 were down-regulated in colorectal tissues of LST patients, the expression of P53 is up-regulated, they may participate in the occurrence and development of LST, especially LST-NG.
[Objective]To observe the expression of PTEN, P53 and P16 proteins in laterally spreading tumor(LST) and their three subtypes, and to explore their roles in the development of LST. [Methods]90 cases of colorectal tissues resected by endoscopic submucosal dissection were selected as group LST, another 80 cases of protruded-type colorectal adenoma(PA) resected by ESD at the same time were selected as PA group, and 70 cases of normal colorectal tissues of patients without organic lesions in the whole colon examined by colonoscopy as control group. 90 cases of LST were divided into 3 groups, 27 cases of granular homogeneous type(LST-G-H), 25 cases of nodular mixed type(LST-G-M) and 38 cases of non-granular type(LST-NG) and their clinical data were compared; the levels of PTEN, P53 and P16 were detected by immunohistochemical method(SP). [Results]The lesion diameter of LST and three subtypes patients was significantly larger than that of PA patients(P<0.05). LST lesions are mostly distributed in the rectum, PA lesions mostly located in distal colon and the difference between them is significant(P<0.05). The proportion of histological types in LST patients was villous adenoma, tubular villous adenoma, tubular adenoma and serrated adenoma in turn; tubular adenomas accounted for the highest proportion of PA lesions, and there was no serrated adenoma; villous adenoma was the predominant lesion in LST-G-H and LST-G-M, tubular villous adenoma accounts for the highest proportion in LST-NG. The canceration rate of LST was significantly higher than that of PA(P<0.05). The expression of PTEN and P16 protein in LST patients was the lowest, followed by PA patients and the highest in control group; the expression of P53 protein was highest in LST patients, followed by PA patients and the lowest in control group. The expression of PTEN protein in LST-NG patients was significantly lower than that in LST-G-H and LST-G-M groups(P<0.05), the positive rates of P53 and P16 protein were significantly higher than those of LST-G-H and LST-G-M groups(P<0.05). [Conclusion]The expression of PTEN and P16 were down-regulated in colorectal tissues of LST patients, the expression of P53 is up-regulated, they may participate in the occurrence and development of LST, especially LST-NG.
引文
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[10] 谢丹阳,吴斌文,李东风,等.衰老标志物在大肠腺瘤和大肠癌中的表达及意义[J].广东医学,2017,38(24):3803-3808.
[11] 吴杰,霍继荣,王东,等.Wnt及整合素信号通路在大肠侧向发育型肿瘤中的表达及与其内镜内镜形态学之间的关系[J].南方医科大学学报,2017,37(9):1234-1241.
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[13] 高志强,张学松,宋毓飞,等.结直肠侧向发育型肿瘤的诊治分析(附17例报告)[J].中国内镜杂志,2017,23(9):103-107.
[14] Imai K,Hotta K,Yamaguchi Y,et al.Preoperative indicators of failure of en bloc resection or perforation in colorectal endoscopic submucosal dissection:implications for lesion stratification by technical difficulties during stepwise training[J].Gastrointest Endosc,2016,83(5):954-962.
[15] 严晓丽,苏永志,杜梦楠,等.大肠癌组织PTEN表达变化及意义[J].山东医药,2017,57(8):61-63.
[16] 王哲,秦宝丽,孙玉秀,等.复发转移大肠癌患者血清PTEN、COX2蛋白表达的研究[J].癌症进展,2017,15(3):283-286.
[17] Ke TW,Wei PL,Yeh KT,et al.MiR-92 a Promotes Cell Metastasis of Colorectal Cancer Through PTEN-Mediated PI3 K/AKT Pathway[J].Ann Surg Oncol,2015,22(8):2649-2655.
[18] 姜忠敏,郑末,张立东,等.大肠癌中B细胞异位基因-2的异常表达及其抑癌机制[J].广东医学,2016,37(14):2169-2172.
[19] Yamaguchi A,Kurosaka Y,Fushida S,et al.Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis[J].Cancer,2015,70(12):2778-2784.
[20] Veganzones S,Maestro ML,Rafael S,et al.Combined methylation of p16 and hMLH1(CMETH2)discriminates a subpopulation with better prognosis in colorectal cancer patients with microsatellite instability tumors[J].Tumor Biol,2015,36(5):1-9.
[2] Okada M,Sakamoto H,Takezawa T,et al.Laterally Spreading Tumor of the Rectum Delineated with Linked Color Imaging Technology[J].Clin Endosc,2016,49(2):207-208.
[3] Ahearn TU,Pettersson A,Ebot EM,et al.A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer[J].J Natl Cancer Inst,2016,108(2):939-939.
[4] 赵喜连,郗彦凤,白文启,等.错配修复蛋白和p53蛋白表达与结直肠癌的临床病理关系及其相关性[J].临床与实验病理学杂志,2016,32(4):370-374.
[5] Zafereo ME,Xu L,Dahlstrom KR,et al.Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus[J].Oral Oncol,2016,56(1):47-53.
[6] 余强,张金坤,袁健,等.大肠侧向发育型肿瘤的内镜下不同治疗方法探讨[J].中华消化内镜杂志,2016,33(6):403-404.
[7] Sakai E,Fukuyo M,Matsusaka K,et al.TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors[J].Cancer Sci,2016,107(6):820-827.
[8] Qi H,Lou M,Chen Y,et al.Non-enzymatic action of RRM1 protein upregulates PTEN leading to inhibition of colorectal cancer metastasis[J].Tumor Biol,2015,36(6):4833-4842.
[9] Li H,Jiang X,Niu X.Long Non-Coding RNA Reprogramming(ROR)Promotes Cell Proliferation in Colorectal Cancer via Affecting P53[J].Med Sci Monit,2017,23(1):919-928.
[10] 谢丹阳,吴斌文,李东风,等.衰老标志物在大肠腺瘤和大肠癌中的表达及意义[J].广东医学,2017,38(24):3803-3808.
[11] 吴杰,霍继荣,王东,等.Wnt及整合素信号通路在大肠侧向发育型肿瘤中的表达及与其内镜内镜形态学之间的关系[J].南方医科大学学报,2017,37(9):1234-1241.
[12] Hayashi Y,Shinozaki S,Sunada K,et al.Efficacy and safety of endoscopic submucosal dissection for superficial colorectal tumors more than 50 mm in diameter[J].Gastrointest Endosc,2016,83(3):602-607.
[13] 高志强,张学松,宋毓飞,等.结直肠侧向发育型肿瘤的诊治分析(附17例报告)[J].中国内镜杂志,2017,23(9):103-107.
[14] Imai K,Hotta K,Yamaguchi Y,et al.Preoperative indicators of failure of en bloc resection or perforation in colorectal endoscopic submucosal dissection:implications for lesion stratification by technical difficulties during stepwise training[J].Gastrointest Endosc,2016,83(5):954-962.
[15] 严晓丽,苏永志,杜梦楠,等.大肠癌组织PTEN表达变化及意义[J].山东医药,2017,57(8):61-63.
[16] 王哲,秦宝丽,孙玉秀,等.复发转移大肠癌患者血清PTEN、COX2蛋白表达的研究[J].癌症进展,2017,15(3):283-286.
[17] Ke TW,Wei PL,Yeh KT,et al.MiR-92 a Promotes Cell Metastasis of Colorectal Cancer Through PTEN-Mediated PI3 K/AKT Pathway[J].Ann Surg Oncol,2015,22(8):2649-2655.
[18] 姜忠敏,郑末,张立东,等.大肠癌中B细胞异位基因-2的异常表达及其抑癌机制[J].广东医学,2016,37(14):2169-2172.
[19] Yamaguchi A,Kurosaka Y,Fushida S,et al.Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis[J].Cancer,2015,70(12):2778-2784.
[20] Veganzones S,Maestro ML,Rafael S,et al.Combined methylation of p16 and hMLH1(CMETH2)discriminates a subpopulation with better prognosis in colorectal cancer patients with microsatellite instability tumors[J].Tumor Biol,2015,36(5):1-9.