Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma
Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma
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DOI：
10.1016/s0002-9440(10)64520-8
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发表时间：
2000-07-01
影响因子：
6
通讯作者：
Rüschoff, J
中科院分区：
文献类型：
--
作者：
Heinmöller, E;Dietmaier, W;Rüschoff, J
关于浸润性导管性胰腺癌周围导管内病变中抑癌基因失活的数据很少或没有。采用一种新型的改良引物延伸和前扩增聚合酶链反应，我们分析了胰腺癌（n = 29）及其相应的胰腺导管内病变（PIL, n = 331）的显微解剖石蜡包埋标本（n = 29），通过微卫星分析检测了p16（INK4）、DPC4和p53的杂合性缺失（LOH），并通过免疫组织化学检测了p53蛋白。22个信息性肿瘤中有9个（41%）存在P16（INK4）位点（9p21）缺失，25个肿瘤中有15个（60%）存在DPC4位点（18q21.1）缺失，27个肿瘤中有22个（81%）存在p53位点（17p13）的P16（INK4）纯合缺失；22个肿瘤中有8个（36%）和25个肿瘤中有4个（16%）仅发现DPC4。此外，29个肿瘤中有24个（83%）显示出相当大的肿瘤内遗传异质性。在具有适合微卫星分析的DNA的277例pil中，有165例（60%）发现至少有一个肿瘤抑制基因发生改变，在单个pil中，仅检测到多达三个改变，p53 LOH甚至发生在肿瘤附近形态正常的导管上皮中。尽管三种肿瘤抑制基因缺失仅在无核异型性的pls中发现，但与DPC4和p53相比，这些病变中p16（INK4）的LOH倾向于更早，肿瘤中的LOH伴p53免疫组化阳性的比例为81%，而在pls中仅为38%。
Little or no data exist concerning the Inactivation of tumor suppressor genes in intraductal lesions surrounding invasive ductal pancreatic carcinomas. Using a novel improved primer extension and preamplification polymerase chain reaction, we analyzed microdissected paraffin-embedded specimens of pancreatic carcinoma (n = 29) and their corresponding pancreatic intraductal lesions (PIL, n = 331) for loss of heterozygosity (LOH) of p16(INK4) DPC4, and p53 by microsatellite analysis and for p53 protein by immunohistochemistry. LOH at the P16(INK4) locus (9p21) mas found in nine of 22 informative tumors (41%), in 15 of 25 tumors (60%) at the DPC4 locus (18q21.1), and In 22 of 27 tumors (81%) at the p53 locus (17p13), Homozygous deletions of p16(INK4); and DPC4 mere found in eight of 22 (36%) and four of 25 tumors (16%), respectively. Furthermore, 24 of 29 tumors (83%) revealed considerable intratumoral genetic heterogeneity. In 165 of 277 PILs (60%) having suitable DNA for microsatellite analysis, alterations In at least one tumor suppressor gene were found, in individual PILs, up to three alterations mere detected, and p53 LOH, occurred even in morphologically normal-appearing ductal epithelium near the tumor. Although deletions of all three tumor suppressor genes mere found in PILs without nuclear atypia, there was a tendency toward earlier LOH of p16(INK4) compared to DPC4 and p53 in these lesions, LOH in tumors accompanied positive P53 immunohistochemistry in 81% but only in 38% in PILs.