title: Clinical Significance of Substaging and HER2 Expression in Papillary Nonmuscle Invasive Urothelial Cancers of the Urinary Bladder.
abstract: The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC.
authors.affiliation: Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: So Dug
authors.initials: SD
authors.lastname: Lim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yong Mee
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Gyu-Seog
authors.initials: GS
authors.lastname: Choi
authors.affiliation: Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Hyung Kyu
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Paick
authors.affiliation: Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Wook Youn
authors.initials: WY
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Soo-Nyung
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Ghilsuk
authors.initials: G
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Bladder Cancer; Cancer Staging; HER2 Gene; Immunohistochemistry; In Situ Hybridization