title: Molecular and immunohistologic analyses cannot reliably solve diagnostic variation of flat intraepithelial lesions of the urinary bladder.
abstract: We examined diagnostic variation of flat intraurothelial lesions with comparison with immunohistochemical and fluorescence in situ hybridization (FISH) analyses. Nine uropathologists diagnosed 23 biopsy samples from the urinary bladder. The samples were analyzed by immunohistochemical expression of cytokeratin 20, high-molecular-weight cytokeratin, Ki-67, p53, and p16(INK4a), and multicolor FISH using the UroVysion probe set (Vysis, Abbott, Des Plaines, IL). Diagnostic agreement for each classification and for nonneoplastic or neoplastic lesions was obtained in 8 (35%) and 16 (70%) of 23 lesions, respectively. The preference ratio of neoplasia to nonneoplasia (0.9 to 4.8) or carcinoma in situ to dysplasia (0.2 to 4.0) also varied among the pathologists. In 6 ancillary analyses, the majority of neoplastic lesions with diagnostic agreement indicated more than 2 aberrant results, whereas the majority of lesions without diagnostic agreement showed no or only 1 aberrant result. The molecular and immunohistochemical analyses can discriminate between neoplastic and nonneoplastic lesions; however, they cannot reliably solve diagnostic variation of flat intraepithelial lesions.
authors.affiliation: Department of Pathology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama-ken, 350-1298, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Murata
authors.forename: Masachika
authors.initials: M
authors.lastname: Iseki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kinjo
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuzaki
authors.forename: Akira
authors.initials: A
authors.lastname: Moriuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtani
authors.forename: Takaki
authors.initials: T
authors.lastname: Sakurai
authors.forename: Tatsunari
authors.initials: T
authors.lastname: Satake
authors.forename: Toyonori
authors.initials: T
authors.lastname: Tsuzuki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D053554:Keratin-20 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D053554:Keratin-20; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53