Intestinal metaplasia (IM) is a rare finding in urinary bladder specimens. It is unclear whether IM without dysplasia is a precursor of malignancy in the urinary system. We retrospectively selected 9 cases of IM of bladder (1 case harboring high-grade dysplasia), and performed mutation analysis for genes frequently mutated in colon cancer including BRAF, APC, KRAS, MET, NRAS, PIK3CA, CTNNB1, FBXW7, and TP53 using validated clinical tests. Control groups included 7 colonic tubular adenomas, 10 high-grade papillary urothelial carcinomas. One IM case revealed an APC mutation and another showed an NRAS mutation. Among the tubular adenomas cases, 6 of 7 (85.7%) harbored KRAS mutations and 3 of 7 (42%) APC mutations. Among urothelial carcinomas cases, 1 revealed a KRAS mutation, 2 had PIK3CA mutations, and all cases were negative for APC mutations. Clinical follow-up for the IM patients was available with a median follow-up of 70 months. One patient—without any mutation in the genes investigated—developed invasive bladder adenocarcinoma with intestinal differentiation with metastasis to the liver and lung. Neither of the 2 patients harboring mutations developed any malignancy. In conclusion, a minority of cases with IM without dysplasia bear mutations in the genes commonly associated with colonic adenocarcinoma, suggesting a premalignant potential for such lesions possibly following the classic multistep chromosomal instability pathway of carcinogenesis. A larger cohort of patients with longer follow-up is needed to better establish whether close follow-up is warranted for mutation-harboring IM of the bladder.

中文翻译：

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膀胱无发育异常的肠化生分析仅揭示与结直肠腺癌相关的罕见突变

肠化生（IM）在膀胱标本中很少见。目前尚不清楚无发育异常的 IM 是否是泌尿系统恶性肿瘤的前兆。我们回顾性选择了 9 例膀胱 IM 病例（1 例患有重度不典型增生），并对结肠癌中经常突变的基因（包括 BRAF、APC、KRAS、MET、NRAS、PIK3CA、CTNNB1、FBXW7 和 TP53）进行了突变分析。经验证的临床试验。对照组包括 7 例结肠管状腺瘤、10 例高级别乳头状尿路上皮癌。一个 IM 病例显示 APC 突变，另一个显示 NRAS 突变。在管状腺瘤病例中，7 例中有 6 例 (85.7%) 携带 KRAS 突变，7 例中有 3 例 (42%) APC 突变。尿路上皮癌中，1例KRAS突变，2例PIK3CA突变，所有病例APC突变均为阴性。IM 患者的临床随访时间为 70 个月。一名患者（在所研究的基因中没有任何突变）发展为浸润性膀胱腺癌，伴有肠分化并转移至肝和肺。两名携带突变的患者均未发生任何恶性肿瘤。总之，少数无异型增生的 IM 病例在通常与结肠腺癌相关的基因中存在突变，这表明此类病变可能遵循经典的致癌多步染色体不稳定性途径的癌前病变。需要更大的随访时间更长的患者队列，以更好地确定是否需要对携带突变的膀胱 IM 进行密切随访。