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REG4 is associated with carcinogenesis in the |[lsquo]|intestinal|[rsquo]| pathway of intraductal papillary mucinous neoplasms

机译:REG4与| [|肠||肠|||]的癌变相关导管内乳头状黏液性肿瘤的通路

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Subclassification of intraductal papillary mucinous neoplasms of the pancreas (IPMNs), based on morphological features and immunohistochemical profiles, has been proposed. Intestinal-type IPMNs frequently show moderate to severe dysplasia. Regenerating islet-derived family, member 4 (REG4) is associated with the adenoma-carcinoma sequence in colon cancer and it is also associated with intestinal phenotype. Therefore, to identify REG4 expression in IPMNs may be helpful to detect high-grade IPMNs. We also investigated REG4 expression and CDX2 expression in IPMNs. To investigate the expressions of REG4 and CDX2 in IPMNs and in invasive ductal adenocarcinoma derived from IPMN, we used immunohistochemical staining and microdissection-based quantitative real-time reverse transcription-polymerase chain reaction. Among 125 IPMNs, 43 (34%) were positive for REG4 and most of the intestinal-type IPMNs showed its expression (35/38). The positive ratio of REG4 expression in colloid carcinoma (5/7) was significantly higher than that in tubular carcinoma (1/17; P=0.003). Most of CDX2-positive cases (31/33) expressed REG4 protein, whereas only 12 of 92 CDX2-negative cases did (PREG4 mRNA in intestinal-type IPMN were significantly higher compared to those in gastric-type IPMN or to normal pancreatic ductal epithelium (P=0.005, P=0.004, respectively). REG4 expression was observed more frequently in borderline lesions (14/28) and carcinoma (21/45) compared to adenoma (8/52). Using the Ki-67 labeling index, REG4 expression was significantly correlated with proliferative activity in borderline lesions. We conclude that REG4 is involved in the ‘intestinal’ pathway of carcinogenesis in IPMN.
机译:已经提出了基于形态学特征和免疫组织化学特征的胰腺导管内乳头状粘液性肿瘤(IPMN)的亚分类。肠型IPMN经常显示中度至严重的不典型增生。再生胰岛来源的家族,成员4(REG4)与结肠癌中的腺瘤-癌序列有关,也与肠道表型有关。因此,识别IPMN中的REG4表达可能有助于检测高级IPMN。我们还调查了IPMN中的REG4表达和CDX2表达。为了研究REG4和CDX2在IPMNs和IPMN衍生的浸润性导管腺癌中的表达,我们使用了免疫组织化学染色和基于显微解剖的实时定量逆转录聚合酶链反应。在125个IPMN中,有REG4阳性的有43个(34%),大多数肠型IPMN都显示了它的表达(35/38)。胶体癌中REG4表达的阳性率(5/7)明显高于肾小管癌(1/17; P = 0.003)。大多数CDX2阳性病例(31/33)表达REG4蛋白,而92例CDX2阴性病例中只有12种表达(肠型IPMN中的PREG4 mRNA显着高于胃型IPMN或正常胰管上皮细胞) (分别为P = 0.005,P = 0.004)。与腺瘤(8/52)相比,在边缘性病变(14/28)和癌(21/45)中观察到REG4的表达更为频繁。使用Ki-67标记指数, REG4的表达与边界病变中的增殖活性显着相关,我们得出结论,REG4参与了IPMN致癌的“肠道”途径。

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