From the *Department of Human Pathology, Field of Oncology, and †Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University; ‡Department of Pathology, and §Department of Surgery, Kagoshima-shi Medical Association Hospital, Kagoshima, Japan; ∥Departments of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE; and ¶National Sanatorium Hoshizuka-Keiaien, Kanoya, Kagoshima, Japan.
Pancreas. 2013 Oct;42(7):1120-8. doi: 10.1097/MPA.0b013e3182965915.
This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN).
We performed immunohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of 2 anti-MUC4 monoclonal antibodies, 8G7 and 1G8, in cancer cell lines.
Monoclonal antibody 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 messenger RNA. However, IHC signals detected by both monoclonal antibodies were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced.
A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential.
本研究旨在研究黏蛋白 4(MUC4)在胰腺导管内乳头状黏液性肿瘤(IPMN)中的表达谱。
我们对 142 例 IPMN 进行了 MUC4 的免疫组织化学(IHC)检测,并评估了两种抗 MUC4 单克隆抗体 8G7 和 1G8 在癌细胞系中的特异性。
在表达 MUC4 信使 RNA 的人胰腺癌细胞系中,单克隆抗体 8G7 在 Western blot 和 IHC 中显示出清晰的免疫反应性,而 MAb 1G8 则没有显示出任何免疫反应性。然而,两种单克隆抗体检测到的 IHC 信号均在组织标本中观察到。在肠型 IPMN 中,由 MAb 8G7 检测到的 MUC4/8G7 和由 MAb 1G8 检测到的 MUC4/1G8 的表达率明显高于胃型 IPMN。在肠型 IPMN 中,MUC4/8G7 主要表达在肿瘤细胞的细胞质中,而 MUC4/1G8 主要表达在细胞顶端。即使在低级别异型增生中 MUC4 表达很少的胃型 IPMN 中,当异型增生进展时,两种 MUC4 的表达率均增加。
肠型 IPMN 中 MUC4 的表达明显高于胃型 IPMN,这可能成为区分高恶性潜能肠型 IPMN 和低恶性潜能胃型 IPMN 的生物标志物之一。