Ki-67、p53、P504s在胃癌前病变和早期胃癌中的表达及其意义
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摘要
背景:胃癌的发生是多因素、多步骤、逐渐进展的过程,发生细胞学和结构异常的同时常存在某些分子表达的异常,涉及多种癌基因的活化和抑癌基因的失活。目的:探讨Ki-67、p53、P504s在正常胃黏膜、萎缩性胃炎伴肠化生、低级别上皮内瘤变、高级别上皮内瘤变和早期胃癌中的表达及其意义。方法:收集2015年1月—2016年12月南京大学医学院附属鼓楼医院44例正常胃黏膜、44例萎缩性胃炎伴肠化生黏膜、41例低级别上皮内瘤变、38例高级别上皮内瘤变和35例早期胃癌组织,以免疫组化法检测Ki-67、p53、P504s表达。结果:Ki-67、p53、P504s在萎缩性胃炎伴肠化生、低级别上皮内瘤变、高级别上皮内瘤变、早期胃癌中的表达阳性率逐渐上升,且均显著高于正常胃黏膜组织(P <0. 05)。结论:Ki-67、p53、P504s表达与胃癌的发生、发展密切相关,参与了胃癌发生的早期过程,检测上述三种分子标记物有助于判断病变的严重程度和进展趋势,有利于提高胃癌前病变和早期胃癌的检出率。
Background: The occurrence of gastric cancer is a gradual process with multiple factors and multiple steps. In addition to cytological and structural abnormalities,there are abnormal molecular expressions,which involve the activation of many oncogenes and the inactivation of tumor suppressor genes. Aims: To explore the expressions and significance of Ki-67,p53 and P504s in normal gastric mucosa,atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer. Methods: A total of 44 cases of normal gastric mucosa,44 cases of atrophic gastritis with intestinal metaplasia,41 cases of low-grade intraepithelial neoplasia,38 cases of high-grade intraepithelial neoplasia and 35 cases of early gastric cancer from Jan. 2015 to Dec. 2016 at the Affiliated Drum Tower Hospital of Nanjing University Medical School were collected. Expressions of Ki-67,p53 and P504s were detected by immunohistochemical staining. Results: Compared with normal gastric mucosal tissue,the positivity rates of expression of Ki-67,p53 and P504s in atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer were obviously increased (P < 0. 05). With the increasing of severity of the lesion,the positivity rate gradually increased. Conclusions: The expressions of Ki-67,p53 and P504s are closely related to the occurrence and development of gastric cancer,and are involved in the early process of gastric cancer. The detections of these molecular markers are helpful for determining the severity and trend of the lesion,and beneficial for improving the detection rates of gastric precancerous lesion and early gastric cancer.
Background: The occurrence of gastric cancer is a gradual process with multiple factors and multiple steps. In addition to cytological and structural abnormalities,there are abnormal molecular expressions,which involve the activation of many oncogenes and the inactivation of tumor suppressor genes. Aims: To explore the expressions and significance of Ki-67,p53 and P504s in normal gastric mucosa,atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer. Methods: A total of 44 cases of normal gastric mucosa,44 cases of atrophic gastritis with intestinal metaplasia,41 cases of low-grade intraepithelial neoplasia,38 cases of high-grade intraepithelial neoplasia and 35 cases of early gastric cancer from Jan. 2015 to Dec. 2016 at the Affiliated Drum Tower Hospital of Nanjing University Medical School were collected. Expressions of Ki-67,p53 and P504s were detected by immunohistochemical staining. Results: Compared with normal gastric mucosal tissue,the positivity rates of expression of Ki-67,p53 and P504s in atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer were obviously increased (P < 0. 05). With the increasing of severity of the lesion,the positivity rate gradually increased. Conclusions: The expressions of Ki-67,p53 and P504s are closely related to the occurrence and development of gastric cancer,and are involved in the early process of gastric cancer. The detections of these molecular markers are helpful for determining the severity and trend of the lesion,and beneficial for improving the detection rates of gastric precancerous lesion and early gastric cancer.
引文
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3马志伟,董丹丹,龚百生,等.P504S在前列腺癌、肾细胞癌和膀胱尿路上皮癌中的表达及临床意义[J].临床与病理杂志,2015,35(7):1276-1281.
4 Box A,Alshalalfa M,Hegazy SA,et al.High alphamethylacyl-Co A racemase(AMACR)is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer[J].Tumour Biol,2016,37(9):12287-12299.
5 Jiang Z,Fanger GR,Banner BF,et al.A dietary enzyme:alpha-methylacyl-Co A racemase/P504S is overexpressed in colon carcinoma[J].Cancer Detect Prev,2003,27(6):422-426.
6 Lee WA.Alpha-methylacyl-Co A-racemase expression in adenocarcinoma,dysplasia and non-neoplastic epithelium of the stomach[J].Oncology,2006,71(3-4):246-250.
7 Koc N,Sahin D,Ayas S.Reevaluation of negative cone biopsy results after a positive cervical biopsy finding[J].JLow Genit Tract Dis,2013,17(2):154-159.
8 Wang L,Zheng L,Wang SY,et al.Clonal analysis of gastric carcinoma and precancerous lesions and its relation to Ki-67 protein expression[J].Neoplasma,2009,56(1):48-55.
9 Saricanbaz I,Karahacioglu E,Ekinci O,et al.Prognostic significance of expression of CD133 and Ki-67 in gastric cancer[J].Asian Pac J Cancer Prev,2014,15(19):8215-8219.
10alik M,Demirci E,Altun E,et al.Clinicopathological importance of Ki-67,p27,and p53 expression in gastric cancer[J].Turk J Med Sci,2015,45(1):118-128.
11 Li Q,Zhu Y,Hou L,et al.C23 promotes tumorigenesis via suppressing p53 activity[J].Oncotarget,2016,7(36):58274-58285.
12 Wang W,Cheng B,Miao L,et al.Mutant p53-R273Hgains new function in sustained activation of EGFRsignaling via suppressing miR-27a expression[J].Cell Death Dis,2013,4:e574.
13祁晓莉,戴洁,乔星,等.胃癌变过程中幽门螺杆菌感染与Ki67和P27蛋白表达的意义[J].临床和实验医学杂志,2013,12(21):1711-1714.
14詹颖瑛,王武玲,钱江虹,等.幽门螺杆菌感染与胃组织中P53的表达及微血管密度形成关系研究[J].中华医院感染学杂志,2015,25(22):5131-5133.
15 Zaika AI.Bacterial Pathogen Helicobacter pylori:A Bad AKTor Inhibits p53 Protein Activity[J].Dig Dis Sci,2015,60(4):822-823.
16温爽,盖宇,宗华凤,等.前列腺癌组织P504S、E-Cadherin和bcl-2蛋白表达及意义[J].大连医科大学学报,2013,35(2):123-126.
17 Huang W,Zhao J,Li L,et al.a-Methylacyl coenzyme Aracemase is highly expressed in the intestinal-type adenocarcinoma and high-grade dysplasia lesions of the stomach[J].Histol Histopathol,2008,23(11):1315-1320.
18黄文斌,黄悦,李俐,等.AMACR/P504S在胃黏膜高度异型增生诊断中的价值[J].临床与实验病理学杂志,2012,28(4):367-370.
19吴凤婷,高杰,霰爱兰,等.胃镜活检联合检测P504S在早期胃癌诊断中的价值[J].中华消化病与影像杂志,2013,3(6):294-298.
20陆勤平,黄文斌,刘家祥,等.AMACR/P504s在胃癌中的表达及其临床意义[J].实用医学杂志,2012,28(16):2682-2684.
21李媛.胃粘膜不典型增生性肠化及异型增生:形态学和分子生物学研究[D].北京:北京协和医学院,2012.
2 Bosman F,Carneiro F,Hruban R,et al.WHOclassification of tumors of the digestive system[M].Lyon:IARC Press,2010.
3马志伟,董丹丹,龚百生,等.P504S在前列腺癌、肾细胞癌和膀胱尿路上皮癌中的表达及临床意义[J].临床与病理杂志,2015,35(7):1276-1281.
4 Box A,Alshalalfa M,Hegazy SA,et al.High alphamethylacyl-Co A racemase(AMACR)is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer[J].Tumour Biol,2016,37(9):12287-12299.
5 Jiang Z,Fanger GR,Banner BF,et al.A dietary enzyme:alpha-methylacyl-Co A racemase/P504S is overexpressed in colon carcinoma[J].Cancer Detect Prev,2003,27(6):422-426.
6 Lee WA.Alpha-methylacyl-Co A-racemase expression in adenocarcinoma,dysplasia and non-neoplastic epithelium of the stomach[J].Oncology,2006,71(3-4):246-250.
7 Koc N,Sahin D,Ayas S.Reevaluation of negative cone biopsy results after a positive cervical biopsy finding[J].JLow Genit Tract Dis,2013,17(2):154-159.
8 Wang L,Zheng L,Wang SY,et al.Clonal analysis of gastric carcinoma and precancerous lesions and its relation to Ki-67 protein expression[J].Neoplasma,2009,56(1):48-55.
9 Saricanbaz I,Karahacioglu E,Ekinci O,et al.Prognostic significance of expression of CD133 and Ki-67 in gastric cancer[J].Asian Pac J Cancer Prev,2014,15(19):8215-8219.
10alik M,Demirci E,Altun E,et al.Clinicopathological importance of Ki-67,p27,and p53 expression in gastric cancer[J].Turk J Med Sci,2015,45(1):118-128.
11 Li Q,Zhu Y,Hou L,et al.C23 promotes tumorigenesis via suppressing p53 activity[J].Oncotarget,2016,7(36):58274-58285.
12 Wang W,Cheng B,Miao L,et al.Mutant p53-R273Hgains new function in sustained activation of EGFRsignaling via suppressing miR-27a expression[J].Cell Death Dis,2013,4:e574.
13祁晓莉,戴洁,乔星,等.胃癌变过程中幽门螺杆菌感染与Ki67和P27蛋白表达的意义[J].临床和实验医学杂志,2013,12(21):1711-1714.
14詹颖瑛,王武玲,钱江虹,等.幽门螺杆菌感染与胃组织中P53的表达及微血管密度形成关系研究[J].中华医院感染学杂志,2015,25(22):5131-5133.
15 Zaika AI.Bacterial Pathogen Helicobacter pylori:A Bad AKTor Inhibits p53 Protein Activity[J].Dig Dis Sci,2015,60(4):822-823.
16温爽,盖宇,宗华凤,等.前列腺癌组织P504S、E-Cadherin和bcl-2蛋白表达及意义[J].大连医科大学学报,2013,35(2):123-126.
17 Huang W,Zhao J,Li L,et al.a-Methylacyl coenzyme Aracemase is highly expressed in the intestinal-type adenocarcinoma and high-grade dysplasia lesions of the stomach[J].Histol Histopathol,2008,23(11):1315-1320.
18黄文斌,黄悦,李俐,等.AMACR/P504S在胃黏膜高度异型增生诊断中的价值[J].临床与实验病理学杂志,2012,28(4):367-370.
19吴凤婷,高杰,霰爱兰,等.胃镜活检联合检测P504S在早期胃癌诊断中的价值[J].中华消化病与影像杂志,2013,3(6):294-298.
20陆勤平,黄文斌,刘家祥,等.AMACR/P504s在胃癌中的表达及其临床意义[J].实用医学杂志,2012,28(16):2682-2684.
21李媛.胃粘膜不典型增生性肠化及异型增生:形态学和分子生物学研究[D].北京:北京协和医学院,2012.