TY - JOUR
T1 - Analysis of Intestinal Metaplasia without Dysplasia in the Urinary Bladder Reveal Only Rare Mutations Associated with Colorectal Adenocarcinoma
AU - Amin, Ali
AU - Murati-Amador, Belkiss
AU - Lombardo, Kara A.
AU - Jackson, Cynthia L.
AU - Grada, Zakaria
AU - Palsgrove, Doreen N.
AU - Matoso, Andres
N1 - Funding Information:
This work was supported by the Department of Pathology and Laboratory Medicine of Lifespan Academic Medical Center and by the Department of Pathology of Johns Hopkins Medical Institutions.
Funding Information:
Received for publication January 2, 2019; accepted August 31, 2019. From the *Department of Pathology, Lifespan Academic Medical Center and Brown University, Providence, RI; Departments of †Pathology; §Urology; ∥Oncology, The Johns Hopkins Medical Institutions; and ‡The Greenberg Bladder Cancer Institute of Johns Hopkins University, Baltimore, MD. A.A. and B.M.-A. are co-first authors. D.N.P. and A.M. are co-senior authors. This work was supported by the Department of Pathology and Labo-ratory Medicine of Lifespan Academic Medical Center and by the Department of Pathology of Johns Hopkins Medical Institutions. The authors declare no conflict of interest. Reprints: Andres Matoso, MD, Johns Hopkins Hospital, Weinberg 2242, 401 N. Broadway, Baltimore, MD 21231-2410 (e-mail: amatoso1@jhmi.edu). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - adenocarcinoma
KW - bladder cancer
KW - intestinal metaplasia
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U2 - 10.1097/PAI.0000000000000812
DO - 10.1097/PAI.0000000000000812
M3 - Article
C2 - 31876604
AN - SCOPUS:85077743220
SN - 1541-2016
VL - 28
SP - 786
EP - 790
JO - Applied Immunohistochemistry and Molecular Morphology
JF - Applied Immunohistochemistry and Molecular Morphology
IS - 10
ER -