Department of Gastroenterology and Hepatology, Kawasaki Medical School, Kurashiki, Japan.
Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
Pancreatology. 2023 Nov;23(7):811-817. doi: 10.1016/j.pan.2023.08.007. Epub 2023 Aug 26.
BACKGROUND/OBJECTIVES: Acinar-to-ductal metaplasia (ADM) has been shown to contribute to the development of pancreatic ductal adenocarcinoma (PDAC) in genetically engineered mouse models, but little is known about whether acinar cell plasticity contributes to carcinogenesis in human PDAC. We aimed to assess whether cancer cells that stain positive for amylase and CK19 (ADM-like cancer cells) are present in human resected PDAC and to investigate their role in tumor progression.
We immunohistochemically investigated the presence of ADM-like cancer cells, and compared the clinical and histological parameters of PDAC patients with and without ADM-like cancer cells.
ADM-like cancer cells were detected in 16 of 60 (26.7%) PDAC specimens. Positive staining for anterior gradient protein 2 (AGR2) was observed in 14 of 16 (87.5%) PDAC specimens with ADM-like cancer cells. On the other hand, the intensity of AGR2 expression (negative, low/moderate or high) was lower in PDAC with ADM-like cancer cells (9/7) than in PDAC without these cells (11/33) (P = 0.032). The presence of ADM-like cancer cells was significantly correlated with increased cell proliferation (P = 0.012) and tended to be associated with MUC1 expression (P = 0.067).
These results indicated that acinar cells may act as the origin of human PDAC, and that their presence may be useful for the stratification of human PDAC to predict prognosis.
背景/目的：腺泡-导管化生（ADM）已被证明有助于基因工程小鼠模型中胰腺导管腺癌（PDAC）的发展，但关于腺泡细胞的可塑性是否有助于人类 PDAC 的癌变知之甚少。我们旨在评估在人切除的 PDAC 中是否存在对淀粉酶和 CK19 呈阳性染色的癌细胞（ADM 样癌细胞），并研究其在肿瘤进展中的作用。
我们通过免疫组织化学方法检测 ADM 样癌细胞的存在，并比较了 PDAC 患者中有无 ADM 样癌细胞的临床和组织学参数。
在 60 例 PDAC 标本中，有 16 例（26.7%）检测到 ADM 样癌细胞。在 16 例有 ADM 样癌细胞的 PDAC 标本中，有 14 例（87.5%）检测到前梯度蛋白 2（AGR2）阳性染色。另一方面，在有 ADM 样癌细胞的 PDAC 中（9/7），AGR2 表达的强度（阴性、低/中或高）低于无这些细胞的 PDAC（11/33）（P=0.032）。ADM 样癌细胞的存在与细胞增殖增加显著相关（P=0.012），并倾向于与 MUC1 表达相关（P=0.067）。
这些结果表明，腺泡细胞可能作为人类 PDAC 的起源，其存在可能有助于对人类 PDAC 进行分层，以预测预后。
