Scarpa Aldo, Orlandini Simonetta, Moore Patrick S, Lemoine Nicholas R, Beghelli Stefania, Baron Antonella, Falconi Massimo, Zamboni Giuseppe
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
ICRF Molecular Oncology Unit, Department of Cancer Medicine, Imperial College School of Medicine, London, UK, UK.
Virchows Arch. 2002 Feb;440(2):155-159. doi: 10.1007/s00428-001-0569-6.
DPC4/Smad4 is inactivated in about 50% of pancreatic ductal cancers. It has been recently reported that this gene is also inactivated in neoplasms arising from pancreatic islet cells, a phenomenon suggested to be related to similar progressions of malignancy found in common ductal cancers. To evaluate this possibility, we analysed 20 metastases of pancreatic endocrine carcinomas and their corresponding primary lesion for inactivation of DPC4 using immunohistochemical staining. In fact, immunohistochemical labelling has been shown to correlate with DPC4 gene status with high sensitivity and specificity. The cancers included 18 nonfunctioning tumours, one gastrinoma and one ViPoma all with liver, nodal and/or adrenal metastases. Seventeen were well-differentiated and three poorly differentiated endocrine carcinomas. Dpc4 expression was absent in only one primary well-differentiated endocrine cancer and its liver metastasis, while all the remaining 19 primary tumours and their metastases stained positive for the protein. All positively staining cases showed diffuse cytoplasmic and nuclear staining in virtually all neoplastic cells. Our data suggest that DPC4 is only rarely involved in pancreatic endocrine tumourigenesis and give further weight to the hypothesis that tumours arising from pancreatic exocrine and endocrine epithelia are genetically distinct.
在大约50%的胰腺导管癌中，DPC4/Smad4基因发生失活。最近有报道称，该基因在胰岛细胞来源的肿瘤中也会失活，这一现象被认为与常见导管癌中发现的类似恶性进展有关。为评估这种可能性，我们采用免疫组化染色分析了20例胰腺内分泌癌转移灶及其相应原发灶中DPC4基因的失活情况。事实上，免疫组化标记已被证明与DPC4基因状态具有高度敏感性和特异性的相关性。这些癌症包括18例无功能性肿瘤、1例胃泌素瘤和1例血管活性肠肽瘤，均伴有肝、淋巴结和/或肾上腺转移。其中17例为高分化内分泌癌，3例为低分化内分泌癌。仅1例高分化内分泌癌原发灶及其肝转移灶中未检测到Dpc4表达，其余19例原发肿瘤及其转移灶的蛋白染色均为阳性。所有阳性染色病例在几乎所有肿瘤细胞中均显示弥漫性胞质和核染色。我们的数据表明，DPC4仅很少参与胰腺内分泌肿瘤的发生，并进一步支持了胰腺外分泌和内分泌上皮来源的肿瘤在基因上存在差异这一假说。
