Differential expression of metastasis-associated genes in papilla of vater and pancreatic cancer correlates with disease stage
Differential expression of metastasis-associated genes in papilla of vater and pancreatic cancer correlates with disease stage
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DOI：
10.1200/jco.2001.19.9.2422
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发表时间：
2001-05-01
影响因子：
45.3
通讯作者：
Büchler, MW
中科院分区：
文献类型：
--
作者：
Friess, H;Guo, XZ;Büchler, MW
目的：Vater乳头癌的预后明显优于胰腺癌.目前尚不清楚这是否是两种恶性肿瘤的肿瘤生物学差异的结果。由于转移的形成是一个关键步骤，在肿瘤的进展和一个消极的预后因素，我们比较了nm 23-H1和KAI 1，两个转移抑制基因的表达，在乳头的乏特癌和胰腺lancer.Patients和方法：分析进行了9个正常人乳头的乏特样本，27乳头的乏特癌，16个正常胰腺样本，和29胰腺癌。采用北方印迹法和原位杂交法检测nm 23-H1和KAI 1的表达。此外，免疫组织化学进行本地化各自的proteins.Results：有nm 23-H1和KAI 1 mRNA的表达水平在正常与癌乳头的乏特样本没有差异。相反，nm 23-H1和KAI 1 RNA表达在胰腺癌的早期肿瘤阶段上调，在晚期肿瘤阶段降低。当通过原位杂交分析nm 23-H1和KAI 1 RNA的表达时，正常的Vater乳头上皮细胞表现出与Vater乳头癌细胞相似的mRNA染色强度。在这些样品中也观察到类似水平的nm 23-H1和KAI 1免疫反应性。与此相反，早期胰腺癌样本表现出更强的nm 23 H1和KAI 1免疫反应比正常对照。结论：nm 23-H1和KAI 1两种抑癌基因在胰腺癌组织中的表达差异可能是导致乳头状癌和胰腺癌发生发展不同的原因之一。我们的研究结果支持了生物学差异而不是早期诊断影响这两种肿瘤实体的不同结果的假设。临床肿瘤学杂志19：2422-2432。(C)2001年，美国临床肿瘤学会。
Purpose: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic lancer.Patients and Methods: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins.Results: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages.Conclusion: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities. J Clin Oncol 19:2422-2432. (C) 2001 by American Society of Clinical Oncology.