Fukushima Noriyoshi, Kikuchi Yoshinao, Nishiyama Takashi, Kudo Akira, Fukayama Masashi
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Mod Pathol. 2008 Aug;21(8):1044-53. doi: 10.1038/modpathol.2008.77. Epub 2008 May 16.
Desmoplasia is a common feature of infiltrating ductal adenocarcinoma of the pancreas. This process is intricately interacted between the host and neoplastic cells. Recently, by transcriptome analysis, periostin was identified as a significantly highly expressed gene in pancreatic stellate cells. To investigate the characteristics of periostin immunodeposition in pancreatic ductal neoplasms, we performed immunohistochemistry and in situ hybridization, focusing on tumor-stromal cells interactions. Eighty-one surgically resected pancreatic lesions, including 35 pancreatic ductal adenocarcinoma, 26 intraductal papillary-mucinous neoplasms, 11 mucinous cystic neoplasms and 9 chronic pancreatitis, were studied. In all ductal adenocarcinomas, periostin deposition was observed in the stroma around the infiltrating cancer on immunohistochemistry. Cellular stroma of mucinous cystic neoplasm, called 'ovarian-type' stroma, did not show periostin deposition. In chronic pancreatitis, most of the staining patterns of periostin were perilobular and meshwork-like. Periostin gene expression was detected solely in the stromal cells on in situ hybridization. Intraductal papillary-mucinous neoplasms were classified into four groups on the basis of the histological grade, namely, adenoma, non-invasive adenocarcinoma, adenocarcinoma with microscopical invasion and with macroscopically evident invasion. In intraductal papillary-mucinous neoplasm, periostin deposition in the periductal stroma increased in frequency and intensity in adenocarcinoma compared with adenomas (P=0.014). Furthermore, our results showed that a higher frequency of periostin deposition was correlated with a higher frequency of 'intestinal phenotype' of proliferating epithelium (P=0.036) and laminin-5gamma2 chain expression (P<0.001) in intraductal papillary-mucinous neoplasm, the latter of which is frequently expressed in invasive carcinoma. This is the first report to describe the periostin immunohistochemistry in intraductal papillary mucinous neoplasm of the pancreas.
促结缔组织增生是胰腺浸润性导管腺癌的一个常见特征。这个过程在宿主细胞和肿瘤细胞之间存在复杂的相互作用。最近，通过转录组分析，骨膜蛋白被确定为胰腺星状细胞中显著高表达的基因。为了研究骨膜蛋白免疫沉积在胰腺导管肿瘤中的特征，我们进行了免疫组织化学和原位杂交，重点关注肿瘤-基质细胞的相互作用。我们研究了81例手术切除的胰腺病变，包括35例胰腺导管腺癌、26例导管内乳头状黏液性肿瘤、11例黏液性囊性肿瘤和9例慢性胰腺炎。在所有导管腺癌中，免疫组织化学显示在浸润癌周围的基质中观察到骨膜蛋白沉积。黏液性囊性肿瘤的细胞性基质，即所谓的“卵巢型”基质，未显示骨膜蛋白沉积。在慢性胰腺炎中，骨膜蛋白的大多数染色模式为小叶周围和网状。原位杂交仅在基质细胞中检测到骨膜蛋白基因表达。导管内乳头状黏液性肿瘤根据组织学分级分为四组，即腺瘤、非浸润性腺癌、显微镜下浸润性腺癌和肉眼明显浸润性腺癌。在导管内乳头状黏液性肿瘤中，与腺瘤相比，腺癌中导管周围基质中的骨膜蛋白沉积频率和强度增加（P = 0.014）。此外，我们的结果表明，在导管内乳头状黏液性肿瘤中，骨膜蛋白沉积的较高频率与增殖上皮的“肠型表型”的较高频率（P = 0.036）和层粘连蛋白-5γ2链表达（P < 0.001）相关，后者在浸润性癌中经常表达。这是第一篇描述胰腺导管内乳头状黏液性肿瘤中骨膜蛋白免疫组织化学的报告。
