Pathological and genetic correlates of apoptosis in the progression of colorectal neoplasia

Pathological and genetic correlates of apoptosis in the progression of colorectal neoplasia
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DOI:
10.1159/000218025
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发表时间:
1997-05-01
期刊:
影响因子:
--
通讯作者:
Ward, R
Ward, R
中科院分区:
其他
文献类型:
--
作者:
Hawkins, N;Lees, J;Ward, R

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目的:细胞凋亡在多种人类肿瘤中很常见,并且已经在体外鉴定了一些控制该过程的遗传事件。本研究的目的是确定结直肠肿瘤中细胞凋亡的频率,并检查其与许多病理参数、p53 肿瘤抑制基因突变的存在以及 bcl-2 癌蛋白过度表达的关系。方法:检查109例结直肠肿瘤(26例腺瘤,83例癌),采用原位末端标记法检测石蜡包埋肿瘤切片中的细胞凋亡,并通过光镜评分。通过免疫组织化学测定p53和bcl-2状态。结果:随着肿瘤的进展,细胞凋亡频率增加,正常粘膜中的凋亡细胞明显少于腺瘤或癌,同样,腺瘤的细胞凋亡少于癌,并且细胞凋亡频率随着Dukes分期的增加而增加,总体上,细胞凋亡频率的变化与bcl-2表达水平呈负相关,但与肿瘤的p53状态无关。结论:结直肠肿瘤中细胞凋亡频率在病程中出现增加。肿瘤进展与 bcl-2 表达下降相关,但不受 p53 基因突变的影响。
Purpose: Apoptosis is commonly observed in a variety of human tumors, and some of the genetic events which control this process have been identified in vitro. The aim of this study was to determine the frequency of apoptosis in colorectal neoplasms, and to examine its relationship to a number of pathological parameters, to the presence of mutations in the p53 tumor suppressor gene, and to overexpression of the bcl-2 oncoprotein. Methods: A total of 109 colorectal neoplasms (26 adenomas, 83 carcinomas) were examined, An in situ end-labelling assay was used to detect apoptosis in paraffin-embedded tumor sections, and scores were determined by light microscopy. The p53 and bcl-2 status were determined by immunohistochemistry. Results: Apoptotic frequency increased with tumor progression, Normal mucosa contained significantly fewer apoptotic cells than adenomas or carcinomas, Similarly, adenomas showed less apoptosis than carcinomas, and the frequency of apoptosis increased with Dukes' stage, Overall, changes in apoptotic frequency were inversely Key Words related to the level of bcl-2 expression, but were not related to Apoptosis the p53 status of the tumors, Conclusions: The frequency of apoptosis in colorectal neoplasia appears to increase in the course of tumor progression in association with a decline in bcl-2 expression, but is not influenced by p53 gene mutations.