Analysis of Intestinal Metaplasia Without Dysplasia in the Urinary Bladder Reveal Only Rare Mutations Associated With Colorectal Adenocarcinoma.
Analysis of Intestinal Metaplasia Without Dysplasia in the Urinary Bladder Reveal Only Rare Mutations Associated With Colorectal Adenocarcinoma.
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DOI：
10.1097/pai.0000000000000812
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发表时间：
2020
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摘要膀胱肠化生是一种罕见的疾病。目前尚不清楚没有发育不良的IM是否是泌尿系统恶性肿瘤的前兆。我们回顾性选择9例膀胱IM（1例伴有高度不典型增生），对结肠癌中常见突变基因BRAF、APC、KRAS、MET、NRAS、PIK3CA、CTNNB1、FBXW7、TP53进行突变分析。对照组为结肠管状腺瘤7例，高级别乳头状尿路上皮癌10例。一个IM病例显示APC突变，另一个显示NRAS突变。7例管状腺瘤中6例（85.7%）存在KRAS突变，7例中3例（42%）存在APC突变。尿路上皮癌1例KRAS突变，2例PIK3CA突变，APC突变均阴性。IM患者的临床随访中位随访时间为70个月。一名患者在研究的基因中没有任何突变，发展为浸润性膀胱腺癌，肠分化并转移到肝和肺。这两个携带突变的病人都没有发展成恶性肿瘤。总之，少数没有发育不良的IM患者携带与结肠腺癌相关的基因突变，这表明这种病变可能遵循经典的多步骤染色体不稳定致癌途径。为了更好地确定是否有必要对携带突变的膀胱IM进行密切随访，需要更大的随访时间更长的患者队列。
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.