胃癌组织中PTEN与突变p53的表达及相关性研究
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摘要
目的:
探讨抑癌基因PTEN和突变p53在胃癌组织中的表达及其与胃癌发生发展、临床病理特征之间的关系。
方法:
应用免疫组织化学方法,检测PTEN和突变型p53蛋白在62例胃癌组织、相应癌旁组织及正常胃黏膜组织中的表达。标本常规脱蜡水化后,进行抗原修复,继以免疫组化试剂盒进行检测。操作步骤按说明书进行。以阳性片及PBS代替一抗设阳性及阴性对照。
结果:
62例胃癌组织中PTEN、突变型p53蛋白的阳性表达率分别为48.39%和45.16%,癌旁组织中PTEN、突变型p53蛋白的阳性表达率为90.32%和14.51%,突变型p53蛋白在正常胃黏膜中阳性表达率为9.68%,PTEN蛋白在正常胃黏膜中全部呈阳性表达。PTEN和突变型p53蛋白在胃癌组织中、癌旁组织中、正常胃黏膜中的表达差别有显著差异(P＜0.05)。PTEN表达与胃癌的临床分期、组织分化程度、有无淋巴结转移、有无远处转移有关(P＜0.05),而与患者的性别、年龄、肿瘤的位置、大小、进展程度等临床病理特征无关(P＞0.05)。胃癌组织中PTEN蛋白的表达与突变型p53蛋白的表达呈负相关(P＜0.05)。
结论:
(1)PTEN蛋白的异常表达与胃癌的发生、发展有关;
(2)PTEN蛋白的表达与胃癌的多种重要临床病理预后因素相关:与胃癌的临床分期、组织分化程度、有无淋巴结转移、有无远处转移有关,PTEN基因可以作为评估胃癌某些生物学特性的辅助指标;
(3)p53蛋白的异常表达与胃癌的发生、发展有关;
(4)PTEN与突变型p53蛋白在胃癌的发生、发展中起协同作用,呈负相关。
Objective:
To study the expression of cancer-suppressing genes, PTEN and mutant type p53, in gastric cancer and their relationship with the occurrence and clinicopathological features of the disease.
Methods:
The expression of PTEN and mutant type p53 protein was detected by immunohistochemistry method in 62 specimens of gastric cancer, corresponging adjacent mucosa of gastric cancer and normal gastric mucosa. After routinely dewaxing and hydration, antigen in specimens proceeded to be repaired according to statement by steps on the immunohistochemistry of kits for testing. The positive biopsy and PBS replaced the first antibody to set up positive and negative control.
Results:
The positive rates of expression of PTEN and mutant type p53 protein in gastric cancer were 48.39% and 45.16%, respectively. Those in corresponding adjacent mucosa of gastric cancer were 90.32% and 14.51%, respectively. The positive rate of mutant type p53 protein in normal gastric mucosa was 9.68%, and PTEN protein expressed in all specimens of normal gastric mucosa. The difference of PTEN and mutant type p53 protein expression was significant between cancer and normal gastric mucosa(P<0.05). The expression of PTEN protein was significantly associated with clinical staging, differentiation level, lymph node metastasis, and distant metastasis; but not with sex, age,tumor location, tumor size and invasion level(P>0.05). The expression of PTEN protein inversely correlated with the expression of mutant type p53 protein.
Conclusion:
(1) The abnormal expression of PTEN protein is related to oncogenesis and progression of gastric cancer.
(2) The expression of PTEN protein is associated with multiple clinicopathological characteristics relevant to prognosis. The expression of PTEN gene was significantly associated with clinical staging, differentiation level, lymph node metastasis, and distant metastasis. It is suggested that the expression phenotype of PTEN gene could be an assistant parameter for the evaluation of some biological behavior of gastric cancer.
(3) The abnormal expression of p53 protein is related to oncogenesis and progression of gastric cancer.
(4) The expression of PTEN protein inversely correlated with the expression of mutant type p53 protein.
探讨抑癌基因PTEN和突变p53在胃癌组织中的表达及其与胃癌发生发展、临床病理特征之间的关系。
方法:
应用免疫组织化学方法,检测PTEN和突变型p53蛋白在62例胃癌组织、相应癌旁组织及正常胃黏膜组织中的表达。标本常规脱蜡水化后,进行抗原修复,继以免疫组化试剂盒进行检测。操作步骤按说明书进行。以阳性片及PBS代替一抗设阳性及阴性对照。
结果:
62例胃癌组织中PTEN、突变型p53蛋白的阳性表达率分别为48.39%和45.16%,癌旁组织中PTEN、突变型p53蛋白的阳性表达率为90.32%和14.51%,突变型p53蛋白在正常胃黏膜中阳性表达率为9.68%,PTEN蛋白在正常胃黏膜中全部呈阳性表达。PTEN和突变型p53蛋白在胃癌组织中、癌旁组织中、正常胃黏膜中的表达差别有显著差异(P＜0.05)。PTEN表达与胃癌的临床分期、组织分化程度、有无淋巴结转移、有无远处转移有关(P＜0.05),而与患者的性别、年龄、肿瘤的位置、大小、进展程度等临床病理特征无关(P＞0.05)。胃癌组织中PTEN蛋白的表达与突变型p53蛋白的表达呈负相关(P＜0.05)。
结论:
(1)PTEN蛋白的异常表达与胃癌的发生、发展有关;
(2)PTEN蛋白的表达与胃癌的多种重要临床病理预后因素相关:与胃癌的临床分期、组织分化程度、有无淋巴结转移、有无远处转移有关,PTEN基因可以作为评估胃癌某些生物学特性的辅助指标;
(3)p53蛋白的异常表达与胃癌的发生、发展有关;
(4)PTEN与突变型p53蛋白在胃癌的发生、发展中起协同作用,呈负相关。
Objective:
To study the expression of cancer-suppressing genes, PTEN and mutant type p53, in gastric cancer and their relationship with the occurrence and clinicopathological features of the disease.
Methods:
The expression of PTEN and mutant type p53 protein was detected by immunohistochemistry method in 62 specimens of gastric cancer, corresponging adjacent mucosa of gastric cancer and normal gastric mucosa. After routinely dewaxing and hydration, antigen in specimens proceeded to be repaired according to statement by steps on the immunohistochemistry of kits for testing. The positive biopsy and PBS replaced the first antibody to set up positive and negative control.
Results:
The positive rates of expression of PTEN and mutant type p53 protein in gastric cancer were 48.39% and 45.16%, respectively. Those in corresponding adjacent mucosa of gastric cancer were 90.32% and 14.51%, respectively. The positive rate of mutant type p53 protein in normal gastric mucosa was 9.68%, and PTEN protein expressed in all specimens of normal gastric mucosa. The difference of PTEN and mutant type p53 protein expression was significant between cancer and normal gastric mucosa(P<0.05). The expression of PTEN protein was significantly associated with clinical staging, differentiation level, lymph node metastasis, and distant metastasis; but not with sex, age,tumor location, tumor size and invasion level(P>0.05). The expression of PTEN protein inversely correlated with the expression of mutant type p53 protein.
Conclusion:
(1) The abnormal expression of PTEN protein is related to oncogenesis and progression of gastric cancer.
(2) The expression of PTEN protein is associated with multiple clinicopathological characteristics relevant to prognosis. The expression of PTEN gene was significantly associated with clinical staging, differentiation level, lymph node metastasis, and distant metastasis. It is suggested that the expression phenotype of PTEN gene could be an assistant parameter for the evaluation of some biological behavior of gastric cancer.
(3) The abnormal expression of p53 protein is related to oncogenesis and progression of gastric cancer.
(4) The expression of PTEN protein inversely correlated with the expression of mutant type p53 protein.
引文
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[2]Li J,Yen C,Liaw D,et al.PTEN,a putative protein tyrosine phosphatase gene mutated in human brain,breast,and prostate cancer[J].Science,1997,275(5308):1943-1947.
[3]Steck PA,Pershouse MA,Jzsser SA,et al.Identificatinn of candidate tumour suppressor gene,MMAC1,at chronkisome 10q23.3 that is mutated in multiple advancedcancers[J].Nat Genet,1997,15(4):356-363.
[4]Li DM,Sun H.TEP1,encoded by a candidate tumor suppressor locus,is a novel protein tyrosine phosphatase regulated by transforming growth factor beta[J].Cancer Res,1997,57(11):2124-2129.
[5]Haupt S,Berger M,Goldberg Z,et al.Apoptosis the p53 network[J].J Cell Sci,2003,116(Pt20):4077-4085.
[6]Yamada KM,Araki M.Tumor suppressor PTEN:modulator of cell singaling,growth,migration and apoptosis.J Cell Sci,2001,114(13):2375-2382.
[7]Leslie NR,Downes CP.PTEN:The down side of PI 3-kinase signaling[J].Cell Signal,2002,14(3):285-295.
[8]Yang L,Kuang LG,Zheng HC,et al.PTEN encoding product:a marker for tumorigenesis and progression of gastric carcinoma[J].World J Gastroenterol,2003,9(1):35-39.
[9]Sato K,Tamura Gen,Tsuchiya T,et al.Analysis of genetic and epigenetic alterations of the PTEN gene in gastric cancer[J].Virchows Arch,2002,440(2):160-165.
[10]Fei G,Ebert MPA,Mawrin C,et al.Reduced PTEN expression in gastric cancer and in the gastric mucosa of gastric cancer relatives[J].Eur J Gastroenterol Hepatol,2002,14(3):297-303.
[11]Tamura G.Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer[J].World J Gastroenterol,2006,12(2):192-198.
[12]Dahia PLM.PTEN,a unique tumor suppressor gene[J].Endocr Relat Cancer,2000,7(2):115-129.
[13]Byun D S,Cho K,Ryu B K.et al.Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma[J].Int J Cancer,2003,104(3):318-327.
[14]Li YL,Tian Z,Wu DY,et al.Loss of heterozygosity on 10q23.3 and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions[J].World J Gastroenterol,2005,11(2):285-288.
[15]李锦毅,郑华川,杨琳,等.胃癌中FIEN异常表达与围基因微卫星的杂合性缺失[J].中华肿瘤杂志,2004,26(7):389-392.
[16]李异玲,何向民,郑华川,等.胃黏膜癌变过程中PTEN基因编码产物的表达及意义[J].世界华人消化杂志,2003,11(9):1294-1296.
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