Ishikawa Daichi, Shimada Mitsuo, Utsunomiya Tohru, Morine Yuji, Imura Satoru, Ikemoto Tetsuya, Arakawa Yusuke, Kanamoto Mami, Iwahashi Shuichi, Saito Yu, Yamada Shinichiro, Miyake Hidenori
Department of Surgery, The University of Tokushima, Tokushima, Japan.
J Gastroenterol Hepatol. 2014 Dec;29(12):2032-7. doi: 10.1111/jgh.12652.
Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN.
We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN.
Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival.
Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05).
Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.
导管内乳头状黏液性肿瘤（IPMN）是一种公认的胰腺肿瘤，其范围从低度发育异常到浸润性癌。上皮-间质转化（EMT）有助于多种癌症的肿瘤进展。此外，Notch信号是促进EMT的重要上游效应器之一。目前，尚不清楚EMT是否会导致IPMN的病理进展。
我们评估了促进EMT的转录因子Twist和B细胞特异性莫洛尼鼠白血病病毒插入位点1（Bmi1）在IPMN中的表达。
本研究纳入了在我院及其附属医院接受手术切除的患者（n = 35）。通过免疫组织化学研究切除标本中EMT标志物Twist、Bmi1、Jagged1和E-钙黏蛋白的蛋白表达。将这些蛋白的表达与临床病理因素和患者生存率进行比较。
分别在40.0%和42.9%的IPMN中观察到Twist和Bmi1的阳性表达。Twist和Bmi1在高级别发育异常（P < 0.05）和浸润性癌（P < 0.05）的IPMN中的表达明显高于低级别发育异常的IPMN。Twist的高表达与Jagged1的表达相关，与E-钙黏蛋白的表达呈负相关（分别为P = 0.06和P < 0.05）。在生存分析中，同时高表达Twist和Bmi1的组复发率明显更高（P < 0.05）。
Twist和Bmi1的表达与IPMN的侵袭性和不良预后相关，其通过可能由Notch信号诱导的EMT促进作用实现。
