Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms - Delineation of an "Intestinal" pathway of carcinogenesis in the pancreas
Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms - Delineation of an "Intestinal" pathway of carcinogenesis in the pancreas
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DOI：
10.1097/00000478-200407000-00001
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发表时间：
2004-07-01
影响因子：
5.6
通讯作者：
Klimstra, DS
中科院分区：
文献类型：
--
作者：
Adsay, NV;Merati, K;Klimstra, DS
虽然导管内乳头状粘液性肿瘤（IPMN）的一般特征及其与其他胰腺肿瘤的区别已经很好地确定，但关于其生物学和治疗的一些问题仍未解决。我们和其他作者已经简要地指出，IPMN中有不同类型的乳头，然而，它们的频率，生物学意义和临床相关性尚不清楚。在这项研究中，研究了74例IPMN中不同乳头状模式与临床、病理和生物学参数的关系，并对CDX 2的表达谱进行了研究。（一种特定的标记物和肠道编程的关键决定因素之一，“和肿瘤抑制因子），（胰腺瘤形成中“侵袭性”表型的标志物）和MUC 2（“肠型粘蛋白”，“惰性”表型的标志物和肿瘤抑制物）。乳头的类型及其与这些参数的关系如下：1）乳头型（米泽氏暗细胞型），类似于绒毛状腺瘤，在74例中有26例（35%）。大多数为原位癌（85%）或交界性癌（15%）。它们往往较大（平均5.5 cm）。大多数表达CDX 2（95%）和MUC 2（92%），但不表达MUC 1（8%）。这种类型更常见于胶体型浸润（16例浸润性癌中有14例为胶体型）。2)胰胆管型，其特征在于树枝状乳头内衬立方细胞类似乳头状肿瘤的胆道，是目前在22%的情况下。这些大多被分级为原位癌（94%）;它们很少表达CDX 2（6%）或MUC 2（19%），但经常显示MUC 1标记（44%）。这种模式更常见于管状型浸润性癌，并有轻微的倾向，更积极的临床过程。3)无效型的特点是丰富的顶端粘蛋白和位于基底核，类似于胃小凹上皮。31%的IPMN有这种类型的乳头，但这种模式也存在于其他IPMN的背景中，并且在大多数病例的囊性成分中也存在。大多数纯空型IPMN缺乏复杂性，因此被归类为腺瘤（48%）。它们往往很小（平均2.6 cm），CDX 2、MUC 1和MUC 2通常为阴性，很少与浸润性癌相关。4)一些IPMN（12%）表现出难以分类的特征，2例具有胰胆和肠型乳头的混合物。总之，IPMN包括病理学和生物学上不同的上皮模式。CDX 2和MUC 2表达对于肠型乳头是相对特异的，证实这些IPMN确实表现出肠分化。它们与胶质癌密切相关，胶质癌也显示出一致的MUC 2和CDX 2表达，支持存在肠致癌途径。这种“化生”途径可能反映了这些IPMN发展中的不同遗传事件，并且肠道分化的存在可能潜在地用于将患者分类和分层为适当的治疗类别。
Although general characteristics of intraductal papillary mucinous neoplasms (IPMNs) and their delineation from other pancreatic tumors have been well established, several issues regarding their biology and management remain unresolved. It has been noted briefly by us and other authors that there are different types of papillae in IPMNs; however, their frequency, biologic significance, and clinical relevance are unknown. In this study, the association of different papillary patterns with clinical, pathologic, and biologic parameters was studied in 74 IPMNs, and the expression profile of CDX2 (a specific marker and one of the key determinants of intestinal "programming," and a tumor suppressor) was determined immunohistochemically in addition to MUC1 (a marker of an "aggressive" phenotype in pancreatic neoplasia) and MUC2 ("intestinal type mucin," a marker of the "indolent" phenotype, and a tumor suppressor). The patterns of papillae identified and their association with these parameters were as follows: 1) The intestinal-type (Yonezawa's dark-cell type), similar to villous adenomas, was seen in 26 of 74 (35%) cases. The majority harbored carcinoma in situ (85%) or borderline atypia (15%). They tended to be large (mean, 5.5 cm). Most expressed CDX2 (95%) and MUC2 (92%) but not MUC1 (8%). This type was more commonly associated with colloid-type invasion (14 of 16 invasive carcinomas were of colloid type). 2) The pancreatobiliary type, characterized by arborizing papillae lined by cuboidal cells resembling papillary neoplasms of the biliary tract, was present in 22% of the cases. These were mostly graded as carcinoma in situ (94%); they rarely expressed CDX2 (6%) or MUC2 (19%) but often showed MUC1 labeling (44%). This pattern was more commonly associated with the tubular type of invasive carcinoma and had a slight tendency for a more aggressive clinical course. 3) The null type was characterized by abundant apical mucin and basally located nuclei, similar to the gastric foveolar epithelium. Thirty-one percent of IPMNs had this type of papillae, but this pattern was also present in the background of other IPMNs and in the cystic components of most cases as well. Most pure null-type IPMNs were devoid of complexity and consequently classified as adenoma (48%). They tended to be small (mean, 2.6 cm), were often negative for CDX2, MUC1, and MUC2, and were rarely associated with invasive carcinoma. 4) Some IPMNs (12%) exhibited features that were difficult to classify, and 2 cases had a mixture of pancreatobiliary and intestinal types of papillae. In conclusion, IPMNs include pathologically and biologically distinct epithelial patterns. CDX2 and MUC2 expression is relatively specific for the intestinal type papillae, confirming that these IPMNs indeed exhibit intestinal differentiation. Their close association with colloid carcinoma, which also shows consistent MUC2 and CDX2 expression, supports the existence of an intestinal pathway of carcinogenesis. This "metaplastic" pathway may reflect different genetic events in the development of these IPMNs, and the presence of intestinal differentiation may potentially be used in prognostication and stratification of patients into appropriate treatment categories.