Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent “urothelial” like alterations while BAC and UAC were characterised by a more “colorectal” like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0–45% of BAC, 0–30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports.

原发性腺性膀胱肿瘤（膀胱腺癌[BAC]、脐尿管腺癌[UAC]、伴腺体分化的尿路上皮癌[UCg]）是罕见的恶性肿瘤，该亚组中的大多数患者的组织学与结直肠腺癌（CORAD）相似。确切的病例数非常低，分子数据有限，而且发病机制仍知之甚少。因此，本研究旨在通过深入分析 BAC（n  = 12）、UAC（n  = 13）、UCg（n  = 11）和非侵袭性腺体病变（n  = 19）来补充现有知识。在 BAC 中，除了 TP53、Wnt、MAP 激酶和 MTOR 通路的已知改变外，还发现了SMAD4、ARID1A和BRAF的突变。与已发表的肌层浸润性膀胱癌（BLCA）和 CORAD 数据相比，UCg 表现出频繁的“尿路上皮”样改变，而 BAC 和 UAC 的特征是更“结直肠”样的突变模式。免疫组织化学显示，任何样本中均未发现 DNA 错配修复缺陷或 PD-L1 肿瘤细胞阳性的证据。根据所使用的抗体，0-45% 的 BAC、0-30% 的 UCg 和 0% UAC 病例表现出表达 PD-L1 的肿瘤相关免疫细胞。单个 BAC (9%, 1/11) 显示 ARID1A 蛋白丢失的证据，两例 UCg (20%, 2/10) 分别显示 SMARCA1 和 PBRM1 丢失。总而言之，我们的数据表明至少部分涉及类似的途径驱动 BAC、UAC 和 CORAD 等腺癌的肿瘤发生，而与其组织起源无关。与之前的报道一致，单例肠化生中TERT和FBXW7的改变进一步表明可能的癌前特征。