Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki‐ras mutations provides evidence of a ductal origin
Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki‐ras mutations provides evidence of a ductal origin
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胰腺未分化癌：中间丝轮廓和 Ki-ras 突变的分析提供了导管起源的证据
作者：
A. Hoorens;K. Prenzel;N. Lemoine;G. Klöppel
胰腺的未分化癌和破骨细胞样巨细胞瘤通常含有肿瘤性导管腺体病灶。为了验证未分化癌和破骨细胞样巨细胞瘤具有导管起源的假设，在一系列的17个未分化癌和两个破骨细胞样巨细胞瘤中研究了免疫细胞化学细胞角蛋白模式以及第12结肠的Ki‐ras突变的频率和类型。将未分化癌和破骨细胞样巨细胞瘤的细胞角蛋白特征与10例导管腺癌、20例腺泡细胞癌、25例神经内分泌肿瘤和15例实性假乳头状瘤中发现的细胞角蛋白特征进行比较。所有未分化癌和破骨细胞样巨细胞瘤至少用一种细胞角蛋白抗体染色，其中13/19例用细胞角蛋白7、8、18和19抗体染色。后一种细胞角蛋白在所有导管腺癌中表达，但仅在15/20的腺泡细胞癌、2/25的神经内分泌肿瘤和1/15的实性假乳头状肿瘤中表达。除细胞角蛋白外，15/19例未分化癌/破骨细胞样巨细胞瘤波形蛋白阳性。在10例未分化癌和1例破骨细胞样巨细胞瘤中发现了密码子12处的Ki-ras突变，从中可以成功扩增DNA。在6个肿瘤中分析了Ki‐ras突变模式，与典型的导管腺癌相对应。在具有导管和间变性成分的肿瘤中，这两种成分显示出相同的突变模式。从这些发现可以得出结论，未分化癌和破骨细胞样巨细胞瘤都属于表现出导管表型的胰腺肿瘤。由于未分化癌和破骨细胞样巨细胞瘤具有相同的细胞角蛋白和Ki‐ras特征，因此它们可能来源于相同的细胞谱系。© 1998 John Wiley & Sons，Ltd。
Undifferentiated carcinomas and osteoclast‐like giant cell tumours of the pancreas commonly contain foci of neoplastic ductal glands. To test the hypothesis that undifferentiated carcinomas and osteoclast‐like giant cell tumours have a ductal origin, the immunocytochemical cytokeratin pattern and the frequency and type of Ki‐ras mutations at colon 12 were studied in a series of 17 undifferentiated carcinomas and two osteoclast‐like giant cell tumours. The cytokeratin features of undifferentiated carcinomas and osteoclast‐like giant cell tumours were compared with those found in 10 ductal adenocarcinomas, 20 acinar cell carcinomas, 25 neuroendocrine tumours, and 15 solid‐pseudopapillary tumours. All undifferentiated carcinomas and osteoclast‐like giant cell tumours stained with at least one cytokeratin antibody, and 13/19 of them with antibodies against cytokeratins 7, 8, 18, and 19. The latter cytokeratins were expressed in all ductal adenocarcinomas, but only in 15/20 acinar cell carcinomas, 2/25 neuroendocrine tumours, and 1/15 solid‐pseudopapillary tumours. In addition to cytokeratin, 15/19 undifferentiated carcinomas/osteoclast‐like giant cell tumours were positive for vimentin. Ki‐ras mutations at codon 12 were found in 10 undifferentiated carcinomas and one osteoclast‐like giant cell tumour from which DNA could be successfully amplified. The Ki‐ras mutation patterns were analysed in six tumours and corresponded to those typical of ductal adenocarcinomas. In tumours with ductal and anaplastic components, both components revealed identical mutation patterns. From these findings, it is concluded that both undifferentiated carcinomas and osteoclast‐like giant cell tumours belong to the pancreatic tumours that show a ductal phenotype. Since undifferentiated carcinomas and osteoclast‐like giant cell tumours share the same cytokeratin and Ki‐ras features, they are probably derived from the same cell lineage. © 1998 John Wiley & Sons, Ltd.