Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations

Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations
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DOI:
10.3748/wjg.v12.i24.3803
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发表时间:
2006-06-28
影响因子:
4.3
通讯作者:
Kusano, Mitsuo
Kusano, Mitsuo
中科院分区:
医学2区
文献类型:
--
作者:
Yamazaki, Kimiyasu;Tajima, Yusuke;Kusano, Mitsuo

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目的:目的:探讨胃癌分化型肿瘤的分化表型与肿瘤侵袭性及基因改变的关系.方法:检测48例胃腺瘤和171例分化型胃癌的分化表型、APC和p53基因突变及微卫星不稳定性(MSI).肿瘤通过检测人胃粘蛋白(HGM)、MUC 6、MUC 2和CD 10的表达来确定分化表型。然后根据上述标记物的免疫阳性将肿瘤分为胃(G-)、胃和肠混合(GI-)或肠(I-)表型。结果:与胃癌相比,胃腺癌与CD 10表达、I型肿瘤和APC突变的存在显著相关(66.7%vs25.1%,P < 0.0001; 56.3%vs14.6%,P < 0.0001; 39.6%vs14.0%,P < 0.0001),与HGM、MUC 6表达及p53突变呈负相关(10.4%vs62.6%,P < 0.0001; 39.6%vs64.3%,P = 0.003; 2.0%vs26.3%,P = 0.001)。APC突变频率在HGM阴性肿瘤、MUC 6阴性肿瘤、CD 10阳性肿瘤和I表型肿瘤中显著高于HGM阳性肿瘤、MUC 6阳性肿瘤、CD 10阴性肿瘤和G表型肿瘤(分别为32.7%vs7.1%,P < 0.0001; 27.8%vs14.0%,P = 0.0182; 37.3%vs10.4%,P < 0.0001; 38.5%vs9.5%,P = 0.0017)。MUC 6阳性、CD 10阴性和G表型肿瘤的MSI发生率显著高于MUC 6阴性、CD 10阳性和I表型肿瘤(24.8%vs6.7%,P = 0.0009; 22.2%vs8.0%,P = 0.0143; 28.6%vs9.6%,P = 0.0353)。结论:胃癌分化型肿瘤的分化表型与肿瘤的侵袭性和基因改变密切相关。(C)2006年,WJG出版社。All rights reserved.
AIM: To clarify the relations between tumor differentiation phenotype and tumor invasion or genetic alterations in gastric differentiated-type tumors.METHODS: We examined the tumor differentiation phenotype, the presence of mutations in APC and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas and 171 differentiated-type carcinomas. The tumor. differentiation phenotype was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10. The tumors were then classified into gastric- (G-), gastric and intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the immunopositivity of the above markers. The presence of mutations in APC and p53 and the MSI status were also investigated in all the tumors.RESULTS: Gastric adenomas were significantly associated with CD10 expression, I-phenotype tumors and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P < 0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and inversely associated with expressions of HGM and MUC6 and the presence of p53 mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%, P = 0.001, respectively). The frequency of APC mutations was significantly higher in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P = 0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively). The frequency of MSI was significantly higher in MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%, P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively).CONCLUSION: The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors. (C) 2006 The WJG Press. All rights reserved.