Park Jason Y, Hong Seung-Mo, Klimstra David S, Goggins Michael G, Maitra Anirban, Hruban Ralph H
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, 75235, USA.
Appl Immunohistochem Mol Morphol. 2011 Oct;19(5):444-9. doi: 10.1097/PAI.0b013e318206d958.
Pancreatic and duodenal homeobox (Pdx1) is a homeobox transcription factor required for the embryonic development of the pancreas. Pdx1 expression has been earlier identified in pancreatic ductal adenocarcinomas and endocrine neoplasms. This study characterizes Pdx1 protein expression in pancreatic precursor lesions and neoplasms, including pancreatic intraepithelial neoplasia (PanIN, n=32), intraductal papillary mucinous neoplasm (IPMN, n=88), mucinous cystic neoplasm (MCN, n=3), acinar cell carcinoma (ACC, n=8), pancreatic endocrine neoplasm (PEN, n=44), pancreatoblastoma (PB, n=1), solid pseudopapillary neoplasm (n=8), invasive ductal adenocarcinoma (n=67), and nondysplastic ductal epithelium. A mouse monoclonal antibody for Pdx1 was used to examine archived surgical pathology cases and tissue microarrays containing >655 tissue cores from more than 250 pancreatic specimens. Immunohistochemical labeling for Pdx1 was performed using standard methods and scored for percentage and intensity of nuclear labeling. Among non-neoplastic pancreatic tissues, Pdx1 nuclear protein was expressed in islet cells, cells of the centroacinar cell compartment, and non-neoplastic ductal epithelium. No expression of Pdx1 was seen in non-neoplastic acinar cells. Among pancreatic neoplasms, Pdx1 consistently labeled >50% of the tumor cells in 87.5% of ACC cases and 38.6% of PEN cases. Pdx1 expression was variable in invasive ductal adenocarcinoma and precursor lesions of ductal adenocarcinomas (PanIN, IPMN, and MCN). A single case of PB was examined and it showed Pdx1 in the acinar component, but no expression in squamoid nests. Solid pseudopapillary neoplasms did not express Pdx1. This study shows Pdx1 expression in precursor lesions of ductal adenocarcinomas, PEN, ACC, and a case of PB. In the immunohistochemical evaluation of neoplasms of the pancreas, Pdx1 expression is not a finding specific to PENs and ductal adenocarcinomas, but also occurs in precursor lesions (PanIN, IPMN, MCN) and other neoplasms of the pancreas.
胰腺十二指肠同源盒基因(Pdx1)是胰腺胚胎发育所需的一种同源盒转录因子。Pdx1的表达最早在胰腺导管腺癌和内分泌肿瘤中被发现。本研究对Pdx1蛋白在胰腺前驱病变和肿瘤中的表达进行了特征分析,包括胰腺上皮内瘤变(PanIN,n = 32)、导管内乳头状黏液性肿瘤(IPMN,n = 88)、黏液性囊性肿瘤(MCN,n = 3)、腺泡细胞癌(ACC,n = 8)、胰腺内分泌肿瘤(PEN,n = 44)、胰母细胞瘤(PB,n = 1)、实性假乳头状肿瘤(n = 8)、浸润性导管腺癌(n = 67)以及非发育异常的导管上皮。使用一种针对Pdx1的小鼠单克隆抗体检查存档的手术病理病例以及包含来自250多个胰腺标本的655个以上组织芯块的组织微阵列。采用标准方法进行Pdx1的免疫组织化学标记,并对核标记的百分比和强度进行评分。在非肿瘤性胰腺组织中,Pdx1核蛋白在胰岛细胞、腺泡中心细胞区的细胞以及非肿瘤性导管上皮中表达。在非肿瘤性腺泡细胞中未见Pdx1表达。在胰腺肿瘤中,Pdx1在87.5%的ACC病例和38.6%的PEN病例中持续标记>50%的肿瘤细胞。Pdx1在浸润性导管腺癌和导管腺癌的前驱病变(PanIN、IPMN和MCN)中的表达存在差异。检查了1例PB,其腺泡成分中显示有Pdx1,但鳞状巢中无表达。实性假乳头状肿瘤不表达Pdx1。本研究显示Pdx1在导管腺癌、PEN、ACC的前驱病变以及1例PB中表达。在胰腺肿瘤的免疫组织化学评估中,Pdx1的表达并非PEN和导管腺癌所特有,也见于前驱病变(PanIN、IPMN、MCN)和胰腺的其他肿瘤。