Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan; Department of Pathology, Saitama International Medical Center, Saitama Medical University, Hidaka, Japan.
J Pathol. 2013 Nov;231(3):335-41. doi: 10.1002/path.4242.
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.
管状绒毛状肿瘤（ITPNs）由胰腺管内具有高级别异型增生的管状绒毛状腺体组成。胃型肠上皮化生型的胰腺导管内乳头状黏液性肿瘤（IPMN-PGs）由类似于幽门腺的管状腺体组成，具有低级别异型增生，以前被称为胰腺导管内管状腺瘤。由于它们具有明显的共同管状形态，因此 IPMN-PGs 和 ITPNs 可能相关。虽然前者可能进展为后者，但这尚未得到充分评估。在这项研究中，我们比较了 14 例 ITPNs 和 15 例 IPMN-PGs 的分子特征，以确定它们的关联，使用了 14 例 ITPNs 和 15 例 IPMN-PGs 的福尔马林固定、石蜡包埋组织。通过 Sanger 测序确定 PIK3CA、GNAS、KRAS 和 BRAF 的体细胞突变。通过免疫组织化学检查磷酸化 AKT 的表达。在 3 例 ITPNs（21.4%）中发现了 PIK3CA 体细胞突变，但在所有 IPMN-PGs 中均未发现（p = 0.0996）。相反，在所有 ITPNs 中均未发现 GNAS 突变，但在 15 例 IPMN-PGs 中有 9 例（60.0%；p < 0.001）。在 1 例 ITPN 和 12 例 IPMN-PGs（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-PGs 中均未发现。ITPNs 中磷酸化 AKT 的表达明显比 IPMN-PGs 更明显（p = 0.0401）。这些结果表明 ITPNs 和 IPMN-PGs 在分子上是不同的，这表明 IPMN-PG 不会进展为 ITPN。此外，还证实了 IPMN-PGs 的分子特征与其他地方报道的 IPMNs 相同。这些结果验证了目前将胰腺管内肿瘤分为 IPMN 和 ITPN 的世界卫生组织系统，并确认 IPMN-PG 不是 ITPN 的良性对应物。术语“胰腺导管内管状腺瘤”应被消除，代之以 IPMN-PG。
