Adenosquamous carcinoma of the pancreas (ASCAP) is characterized by conventional pancreatic ductal adenocarcinoma (PDAC) and squamous carcinoma components with at least 30% of the tumour showing squamous differentiation. To get further insight into the histogenesis of these lesions, we analysed the cellular organization of ASCAP compared to PDACs. Using Immunohistochemistry and triple immunofluorescence labelling studies for keratins, p63, p40, MUC1, MUC2, MUC5AC, Ki67, and EGFR we demonstrate that many ASCAPs contain a transitional zone between the K8/18-positive adenocarcinomatous component and the p63+ /p40+ /K5/K14+ squamous component initiated by the expression of p63 in K8/18+ adenocarcinomatous cells and the appearance of basally located p63+ K5/14+ cells. p63+ K5/14+ cells give rise to fully developed squamous differentiation. Notably, 25% of conventional PDACs without histologically recognizable squamous component contain foci of p63+ p40+ and K5/14+ cells similar to the transitional zone. Our data provide evidence that the squamous carcinoma components of ASCAPs originate from pre-existing PDAC via transdifferentiation of keratin K8/18-positive glandular cells to p63-, p40-, and keratin K5/14-positive squamous carcinoma cells supporting the squamous metaplasia hypothesis. Thus our findings provide new evidence about the cellular process behind squamous differentiation in ASCAPs.

胰腺腺鳞癌（ASCAP）的特征是常规胰腺导管腺癌（PDAC）和鳞癌成分，其中至少30％的肿瘤表现为鳞状分化。为了进一步了解这些病变的组织发生，我们分析了与PDAC相比ASCAP的细胞组织。使用针对角蛋白，p63，p40，MUC1，MUC2，MUC5AC，Ki67和EGFR的免疫组织化学和三重免疫荧光标记研究，我们证明了许多ASCAPs在K8 / 18阳性腺癌成分与p63 + / p40 + / K5 /之间存在一个过渡区。 K14 +鳞状成分由p63在K8 / 18 +腺癌细胞中的表达和基底定位的p63 + K5 / 14 +细胞的出现引起。p63 + K5 / 14 +细胞引起完全发展的鳞状细胞分化。值得注意的是 没有组织学上可识别的鳞状成分的传统PDAC中有25％的p63 + p40 +和K5 / 14 +细胞灶与过渡区相似。我们的数据提供了证据，表明ASCAP的鳞状癌成分是通过将角蛋白K8 / 18阳性腺细胞转分化为支持鳞状化生假说的p63-，p40-和角蛋白K5 / 14阳性鳞状细胞而起源于预先存在的PDAC。 。因此，我们的发现为ASCAP鳞状细胞分化背后的细胞过程提供了新的证据。我们的数据提供了证据，表明ASCAP的鳞状癌成分通过角蛋白K8 / 18阳性腺细胞向p63-，p40-和角蛋白K5 / 14阳性鳞状细胞的转分化而支持P鳞状上皮化生假设的PDAC起源。因此，我们的发现为ASCAP鳞状细胞分化背后的细胞过程提供了新的证据。我们的数据提供了证据，表明ASCAP的鳞状癌成分是通过将角蛋白K8 / 18阳性腺细胞转分化为支持鳞状化生假说的p63-，p40-和角蛋白K5 / 14阳性鳞状细胞而起源于预先存在的PDAC。 。因此，我们的发现为ASCAP鳞状细胞分化背后的细胞过程提供了新的证据。