{"title":"胰腺上皮内瘤变与导管内乳头状粘液瘤的生物学异同。","authors":"Toshiyuki Moriya, Wataru Kimura, Shuho Semba, Fumiaki Sakurai, Ichiro Hirai, Jinfeng Ma, Akira Fuse, Kunihiko Maeda, Mitsunori Yamakawa","doi":"10.1385/IJGC:35:2:111","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.</p><p><strong>Aims: </strong>PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two.</p><p><strong>Methodology: </strong>A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2.</p><p><strong>Results: </strong>Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015).</p><p><strong>Conclusions: </strong>In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.</p>","PeriodicalId":84927,"journal":{"name":"International journal of gastrointestinal cancer","volume":"35 2","pages":"111-9"},"PeriodicalIF":0.0000,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1385/IJGC:35:2:111","citationCount":"32","resultStr":"{\"title\":\"Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.\",\"authors\":\"Toshiyuki Moriya, Wataru Kimura, Shuho Semba, Fumiaki Sakurai, Ichiro Hirai, Jinfeng Ma, Akira Fuse, Kunihiko Maeda, Mitsunori Yamakawa\",\"doi\":\"10.1385/IJGC:35:2:111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.</p><p><strong>Aims: </strong>PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two.</p><p><strong>Methodology: </strong>A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2.</p><p><strong>Results: </strong>Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015).</p><p><strong>Conclusions: </strong>In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.</p>\",\"PeriodicalId\":84927,\"journal\":{\"name\":\"International journal of gastrointestinal cancer\",\"volume\":\"35 2\",\"pages\":\"111-9\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2005-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1385/IJGC:35:2:111\",\"citationCount\":\"32\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of gastrointestinal cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1385/IJGC:35:2:111\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of gastrointestinal cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1385/IJGC:35:2:111","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 32
摘要
背景:自胰腺上皮内瘤变(PanIN)分类发表以来，对胰腺癌前体病变的研究正朝着使用标准化术语的新方向发展。目前很少有研究详细探讨PanIN与导管内乳头状粘液瘤(IPMN)的生物学差异。目的:利用各种指标对形态相似的PanIN和IPMN进行比较，找出两者的异同点。方法:在19例浸润性导管癌和18例IPMN患者中，共发现46个PanINs和37个导管伴IPMN。在免疫组织学上检测这些PanINs和IPMNs的HER2/neu、DPC4/Smad4、Akt/PKB、p53、cyclin A、Ki67、MUC1和MUC2的表达模式。结果:MUC1、MUC2在IPMNadenoma与PanIN-2、CIS与PanIN-3的表达差异有统计学意义(MUC1: p = 0.001、p = 0.005;MUC2: p = 0.002和p < 0.001)。CIS与PanIN-3在p53表达水平上也有显著差异(p = 0.015)。结论:在IPMN和PanIN中，随着HER2/neu、DPC4/Smad4和Akt/PKB的表达增加，异型性等级也随着多期癌变过程的进展而增加。虽然这些因子的表达水平反映了异型性的程度，但它们并没有反映IPMN和PanIN在生物恶性程度上的任何差异。另一方面，MUC1和MUC2可能作为分化方向的指标，即向IDAC或IPMN进展。MUC1的阳性被认为表明分化为IDAC, MUC2的阳性似乎表明分化为IPMN。甚至在HER2/neu、Akt/PKB、DPC4/Smad4、p53和cyclin A表达异常开始检测之前，PanIN1-2似乎就出现了这种分化方向的指示。
Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.
Background: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.
Aims: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two.
Methodology: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2.
Results: Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015).
Conclusions: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.
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