The discrete nature and distinguishing molecular features of pancreatic intraductal tubulopapillary neoplasms and intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant
The discrete nature and distinguishing molecular features of pancreatic intraductal tubulopapillary neoplasms and intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant
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DOI：
10.1002/path.4242
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发表时间：
2013-11-01
影响因子：
7.3
通讯作者：
Furukawa, Toru
中科院分区：
文献类型：
--
作者：
Yamaguchi, Hiroshi;Kuboki, Yuko;Furukawa, Toru
胰管内管状乳头状肿瘤（ITPN）是由胰管内管状乳头状腺体伴高度发育不良组成。胃导管内乳头状粘液性肿瘤幽门腺变异型（IPMN-PGs）是由管状腺体组成的类似幽门腺的低度异型增生的肿瘤，以前称为导管内管状腺瘤。由于它们明显的共同管状形态，IPMN-PG和ITPN可能相关。虽然前者可能会发展为后者，但尚未充分评估。在这项研究中，我们比较了ITPN和IPMN-PG的分子特征，以确定它们的协会使用福尔马林固定，石蜡包埋组织的14 ITPN和15 IPMN-PG。通过桑格测序确定PIK 3CA、GNAS、KRAS和BRAF中的体细胞突变。免疫组化法检测磷酸化AKT的表达。在14个ITPN中的3个（21.4%）中发现了体细胞PIK 3CA突变，但在IPMN-PG中没有发现（p = 0.0996）。相比之下，在ITPN中没有发现GNAS突变，但在15个IPMN-PG中有9个（60.0%; p < 0.001）。在14例ITPN中的1例（7.1%）和15例IPMN-PG中的12例（80.0%; p < 0.001）中检测到KRAS突变。在1例ITPN中发现BRAF突变，但在所有IPMN-PG中均未发现BRAF突变。ITPN中的磷酸化AKT表达比IPMN-PG中的磷酸化AKT表达显著更明显（p = 0.0401）。这些结果表明ITPN和IPMN-PG在分子上是不同的，表明IPMN-PG不会发展为ITPN。此外，IPMN-PGs的分子特征被证实与其他地方报道的IPMNs的分子特征相同。这些结果验证了目前世界卫生组织将胰腺导管内肿瘤分为IPMN和ITPN的系统，并确认IPMN-PG不是ITPN的良性对应物。术语“导管内管状腺瘤”应删除，并替换为IPMN-PG。版权所有（c）2013年英国和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Intraductal tubulopapillary neoplasms (ITPNs) are composed of tubulopapillary glands with high-grade dysplasia in the pancreatic duct. Intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant (IPMN-PGs) are composed of tubular glands mimicking pyloric glands with low-grade dysplasia and were formerly called intraductal tubular adenomas. Because of their apparent common tubular morphology, IPMN-PGs and ITPNs could be associated. While the former might progress to the latter, this has not been fully assessed. In this study, we compared the molecular features of ITPNs and IPMN-PGs to determine their association using formalin-fixed, paraffin-embedded tissues of 14 ITPNs and 15 IPMN-PGs. Somatic mutations in PIK3CA, GNAS, KRAS, and BRAF were determined by Sanger sequencing. Expression of phosphorylated AKT was examined by immunohistochemistry. Somatic PIK3CA mutations were found in 3 of 14 ITPNs (21.4%) but in none of the IPMN-PGs (p = 0.0996). In contrast, GNAS mutations were found in none of the ITPNs but in 9 of 15 IPMN-PGs (60.0%; p < 0.001). KRAS mutations were detected in 1 of 14 ITPNs (7.1%) and 12 of 15 IPMN-PGs (80.0%; p < 0.001). BRAF mutation was found in one ITPN but in none of the IPMN-PGs. Phosphorylated AKT expression in ITPNs was significantly more evident than that in IPMN-PGs (p = 0.0401). These results indicate that ITPNs and IPMN-PGs are molecularly distinct, suggesting that IPMN-PG does not progress to ITPN. Furthermore, the molecular features of IPMN-PGs are confirmed to be identical to those of IPMNs reported elsewhere. These results validate the current World Health Organization system that classifies pancreatic intraductal neoplasms into IPMN and ITPN and confirm that IPMN-PG is not a benign counterpart of ITPN. The term intraductal tubular adenoma' should be eliminated and replaced with IPMN-PG. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.