Cell kinetics and genetic instabilities in differentiated type early gastric cancers with different mucin phenotype

Cell kinetics and genetic instabilities in differentiated type early gastric cancers with different mucin phenotype
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DOI:
10.1053/hupa.2003.2
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发表时间:
2003-01-01
期刊:
影响因子:
3.3
通讯作者:
Kohgo, Y
Kohgo, Y
中科院分区:
医学3区
文献类型:
--
作者:
Shibata, N;Watari, J;Kohgo, Y

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为了阐明分化型胃癌(DGC)细胞表型的生物学影响和分子发病机制,我们研究了DGC早期的细胞动力学和遗传不稳定性。共研究了43例早期胃癌(EGCs)。根据HGM、ConA、MUC 2和CD 10的组合将EGC分为3种表型类别:胃型(G型,n = 11)、普通型(O型,n = 20)和完全肠型(CI型,n = 12)。免疫组化法检测Ki-67抗体、末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法和p53抗体分别检测凋亡指数(PI)、凋亡指数(AI)和p53过表达。采用高分辨率荧光微卫星分析系统检测微卫星不稳定性(MSI)和杂合性丢失(洛)。还进行了MSI癌症中转化生长因子β II型受体(TGF-β RII)和bcl-2相关X(BAX)的移码突变分析。平均AI/PI比值G型为0.04,O型为0.10,CI型为0.13,G型显著低于O型和CI型(分别为P = 0.02和P = 0.001)。3种细胞表型之间MSI和洛的发生率无差异。而MSI的主要类型为G型和O型,其变化剧烈,分布广泛,与癌症危险性增加有关,明显高于CI型(P
To clarify the biological impact and molecular pathogenesis of cellular phenotype in differentiated-type gastric cancers (DGCs), we investigated cell kinetics and genetic instabilities in early stage of DGCs. A total of 43 early gastric cancers (EGCs) were studied. EGCs were divided into 3 phenotypic categories: gastric (G type, n = 11), ordinary (O type, n = 20), and complete intestinal (CI type, n = 12) based on the combination of HGM, ConA, MUC2, and CD10. Proliferative index (PI), apoptotic index (AI), and p53 overexpression were investigated by immunohistochemical staining with anti-Ki-67, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method, and p53 antibody, respectively. Using a high-resolution fluorescent microsatellite analysis system, microsatellite instability (MSI) and loss of heterozygosity (LOH) were examined. Frameshift mutation analysis of transforming growth factor-beta type II receptor (TGF-betaRII) and bcl-2-associated X (BAX) in cancers with MSI was also performed. The mean AI/PI ratio values were 0.04 for G-type, 0.10 for O-type, and 0.13 for CI-type cancers-significantly lower in G type than in O and CI types (P = 0.02 and P = 0.001, respectively). No difference in the incidence of MSI and LOH was seen among the 3 cellular phenotypes. However, the major pattern of MSI, which showed drastic and widely dispersed changes and is related to an increased risk for cancer, was significantly higher in G and O types than in CI type (P