Department of Pathology, Odense University Hospital, Odense, Denmark.
HPB Section, Department of Surgery, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Pathol Res Pract. 2020 May;216(5):152925. doi: 10.1016/j.prp.2020.152925. Epub 2020 Mar 19.
Morphology plays an important role in the distinction of autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC). However, we aimed to determine the utility of immunohistochemical tumor markers to contribute in the distinction of these entities. In surgical specimens with AIP (n = 20), PDAC (n = 20) and normal pancreas (n = 20), the expression of pVHL, maspin, IMP3, S100P and Ki67 was examined. We evaluated intralobular reactive ducts / acinoductal metaplasia (ILDs) and extralobular ducts (ELDs) in AIP, neoplastic glands in PDAC, and ductal epithelium in the normal pancreas, using a five-tiered scoring system. The Ki67 hot spot index (Ki67-HSPI) was determined manually and using automated digital imaging analysis of virtual double stains of Ki67 and CK8. Besides, sequential dual-immunohistochemical staining of maspin/pVHL, maspin/IMP3 and Ki67/maspin was performed in a subset of the specimens. Strong overexpression of IMP3, maspin, S100P and Ki67 and loss of pVHL was observed in PDAC compared to AIP and normal pancreas. In AIP however, focal and weak aberrant expression was observed with the following proportions in ILDs/ELDs: pVHL in 45 %/85 %, maspin in 30 %/70 %, IMP3 in 55 %/5%, S100P in 10 %/35 % and Ki67-HSPI >20 % in 15 %/70 %. At least two markers were aberrantly expressed in ILDs/ELDs in 45 %/60 %. The aberrant expression was more pronounced in type 2 AIP compared to type 1. In conclusion, our data indicate that pVHL, maspin, IMP3, S100P and Ki67 can be focal and weak aberrantly expressed in AIP. However, when used as a panel, these markers seem to be useful for the differentiation of AIP from PC.
形态学在自身免疫性胰腺炎（AIP）与胰腺导管腺癌（PDAC）的鉴别中起着重要作用。然而，我们旨在确定免疫组织化学肿瘤标志物在这些实体鉴别中的效用。在 AIP（n=20）、PDAC（n=20）和正常胰腺（n=20）的手术标本中，检测了 pVHL、maspin、IMP3、S100P 和 Ki67 的表达。我们使用五级评分系统评估 AIP 中的小叶内反应性导管/腺泡间化生（ILDs）和小叶外导管（ELDs）、PDAC 中的肿瘤性腺体和正常胰腺中的导管上皮。使用手动和 Ki67 和 CK8 的虚拟双染色的自动数字成像分析来确定 Ki67 热点指数（Ki67-HSPI）。此外，在一部分标本中进行了 maspin/pVHL、maspin/IMP3 和 Ki67/maspin 的连续双重免疫组织化学染色。与 AIP 和正常胰腺相比，PDAC 中观察到 IMP3、maspin、S100P 和 Ki67 的强烈过表达以及 pVHL 的缺失。然而，在 AIP 中，ILDs/ELDs 中观察到局灶性和弱的异常表达，其比例如下：pVHL 为 45%/85%，maspin 为 30%/70%，IMP3 为 55%/5%，S100P 为 10%/35%，Ki67-HSPI >20%为 15%/70%。在 45%/60%的 ILDs/ELDs 中至少有两种标志物异常表达。在 2 型 AIP 中，异常表达比 1 型更明显。总之，我们的数据表明，pVHL、maspin、IMP3、S100P 和 Ki67 在 AIP 中可能会出现局灶性和弱的异常表达。然而，当作为一个标志物组合使用时，这些标志物似乎可用于 AIP 与 PC 的鉴别。
