Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype
Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype
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DOI：
10.1097/sla.0b013e31828cd008
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发表时间：
2013-07-01
影响因子：
9
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Ideno, Noboru;Ohtsuka, Takao;Tanaka, Masao
目标：为了确定一个高风险组的胰腺导管腺癌（PDAC），独立出现在胰腺导管内乳头状粘液性肿瘤（IPMN），使用组织病理学subtypes.Background：IPMN的病理特征与不同的PDAC，包括组织病理学亚型的IPMN和PDAC表型，还没有得到很好的表征。方法：回顾性分析179例IPMNs和180例无IPMNs的PDACs的临床病理资料。IPMN分为4级（低度、中度、高度异型增生和相关浸润性癌）和4个亚型（胃、肠、胰胆和嗜酸细胞）。通过免疫组织化学研究了MUC 1、MUC 2、MUC 5AC、MUC 6和CDX 2在IPMN和具有和不具有IPMN的PDAC中的表达。结果：在20例（11.2%）IPMNs患者中，共检测到26例同时或异时PDACs。与肠道（1/49，2.0%）、胰胆（1/17，5.9%）或嗜酸细胞型（0/3，0%）相比，胃型IPMN（18/110，16.4%）中合并PDAC的发生率更高（P = 0.047）。通过免疫组织化学评估，具有和不具有IPMN的PDAC经常对MUC 1、MUC 5AC和MUC 6表达呈阳性，但对MUC 2和CDX 2呈阴性。粘蛋白染色模式与胃型IPMNs产生的浸润性管状腺癌相似。在PDAC和胃型IPMNs中未检测到密码子201内的GNAS突变，而其中大多数表现出KRAS突变。然而，R201 H GNAS突变检测在1胰腺型IPMN与不同的PDAC。结论：粘蛋白表达模式表明，PDAC没有GNAS突变的侵略性表型经常出现在胰腺良性胃型IPMN在GNAS突变的情况下。
Objective: To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes.Background: Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types.Methods: Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs.Results: Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC.Conclusions: Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.