title: Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder.
abstract: Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign to primary and secondary malignancies. The accurate diagnosis of these lesions is both important and challenging. Recently, studies suggest that telomerase reverse transcriptase (TERT) promoter mutations could be a biomarker for urothelial carcinoma (UC). We hypothesized that these mutations can distinguish UC with glandular differentiation from nephrogenic adenoma, primary adenocarcinoma of the urinary bladder (PAUB), or secondary malignancies. Twenty-five cases of benign glandular lesions (including nephrogenic adenoma); 29 cases of UC with glandular differentiation; 10 cases of PAUB; and 10 cases each of metastatic colon cancer, prostatic carcinoma, and carcinoma from Mullerian origin were collected. Slides were reviewed and selected to make sure the lesion was at least 10% to 20% of all tissue. Macrodissection was performed in some of cases, and genomic DNA was extracted from the tissue. Telomerase reverse transcriptase promoter mutations were determined by standard polymerase chain reaction sequencing. Twenty-one cases (72%) of UC with glandular differentiation were positive for TERT promoter mutations. However, none of the remaining cases (total 65 cases of benign lesions, PAUB, and metastatic carcinomas) was positive for TERT promoter mutation. Telomerase reverse transcriptase promoter mutations were highly associated with UC including UC with glandular differentiation but not other glandular lesions of bladder. Therefore, in conjunction with morphologic features, Immunohistochemistry stain profile, and clinical information, TERT promoter mutations could distinguish UC with glandular differentiation from other bladder glandular lesions. In addition, lack of TERT promoter mutations in primary adenocarcinoma of bladder suggests that this entity may have different origin or carcinogenesis from those of UC.
authors.affiliation: Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Vail
authors.affiliation: Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, USA.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: NYU Medical Center, New York, NY, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Northwestern University, Chicago, IL, USA.
authors.forename: Ximing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Fallon
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, USA. Electronic address: zhongm@wcmc.com.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhong
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D003556:Cystitis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D001745:Urinary Bladder Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000556:secondary
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase
keywords: Diagnosis; TERT promoter mutation; glandular lesions of urinary bladder