Undifferentiated carcinoma (UC) and undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) are peculiar variants of pancreatic ductal adenocarcinoma (PDAC), characterized by hypercellularity and absence of glandular patterns. The inflammatory microenvironment is peculiar in UCOGC, since it is dominated by macrophages and osteoclast-like giant cells. However, from a molecular point of view, both UC and UCOGC are very similar to conventional PDAC, sharing alterations of the most common genetic drivers. Clinically, UC usually show a worse prognosis, whereas UCOGC may show a better prognosis if it is not associated with a PDAC component. To highlight potential biological differences between these entities, we investigated the role of the epithelial to mesenchymal transition (EMT) in UC and UCOGC. Specifically, we analyzed the immunohistochemical expression of three well-known EMT markers, namely Twist1, Snai2, and E-cadherin, in 16 cases of UCOGC and 10 cases of UC. We found that EMT is more frequently activated in UC (10/10 cases) than in UCOGC (8/16 cases; p = 0.05). Furthermore, in UCOGC, EMT was activated with a higher frequency in cases with an associated PDAC component. Snai2 was the most frequently and strongly expressed marker in both tumor types (10/10 UC, 8/16 UCOGC), and its expression was higher in UC than in UCOGC (mean immunohistochemical score: 4.8 in UC vs. 2.1 in UCOGC, p < 0.01). Our results shed new light on the biology of UC and UCOGC: EMT appeared as a more important process in UC, and Snai2 emerged as a central EMT effector in this setting.

未分化癌 (UC) 和具有破骨细胞样巨细胞的未分化癌 (UCOGC) 是胰腺导管腺癌 (PDAC) 的特殊变体，其特征是细胞过多和腺体模式缺失。UCOGC 的炎症微环境是独特的，因为它以巨噬细胞和破骨细胞样巨细胞为主。然而，从分子的角度来看，UC 和 UCOGC 都与传统的 PDAC 非常相似，共享最常见遗传驱动因素的改变。临床上，UC 通常表现出较差的预后，而 UCOGC 如果与 PDAC 成分无关，则可能表现出更好的预后。为了突出这些实体之间的潜在生物学差异，我们研究了上皮间质转化 (EMT) 在 UC 和 UCOGC 中的作用。具体来说，我们分析了三种众所周知的 EMT 标志物，即 Twist1、Snai2 和 E-钙粘蛋白在 16 例 UCOGC 和 10 例 UC 中的免疫组织化学表达。我们发现 EMT 在 UC（10/10 例）中比在 UCOGC（8/16 例；p  = 0.05）。此外，在 UCOGC 中，在具有相关 PDAC 组件的情况下，EMT 以更高的频率被激活。Snai2 是两种肿瘤类型（10/10 UC，8/16 UCOGC）中最频繁和最强烈表达的标志物，其在 UC 中的表达高于 UCOGC（平均免疫组织化学评分：UC 4.8 vs. UCOGC 2.1，p  < 0.01)。我们的研究结果为 UC 和 UCOGC 的生物学提供了新的线索：EMT 在 UC 中似乎是一个更重要的过程，而 Snai2 在这种情况下成为中心 EMT 效应器。