title: HER2 protein overexpression and gene amplification in upper urinary tract urothelial carcinoma-an analysis of 171 patients.
abstract: Upper urinary tract urothelial carcinomas (UUTUC) are infrequent and show an occurrence of about 5-10% of all urothelial carcinomas. In this study, we investigated the HER2 status of 171 UUTUC patients with nephroureterectomy. The number of patients is the largest of any HER2 study. All 171 cases were analyzed for both HER2 overexpression using immunohistochemistry and HER2 gene amplification using dual-color in situ hybridization. The scoring system proposed by the ASCO/CAP and ToGA trials was used. Out of 171 patients, 140 patients had a HER2 score-0 or score-1 (81.9%), 17 a score-2 (9.9%), and 14 a score-3 (8.2%) with immunohistochemistry. HER2 gene amplification was observed in 31 out of 171 cases (18.1%). A good correlation was observed between protein overexpression and gene amplification (p<0.0001). Twenty-three UUTUC (13.5%) were determined as HER2-positive cancer according to ASCO/CAP and ToGA criteria. HER2 positivity in patients over 70 years old was higher than that of patients under 70 years old (p=0.0132). HER2 expression correlated to a high histological grade (p=0.0003) and the coexistence of a high grade carcinoma in situ (p=0.0089). No HER2-positive cancer was observed in patients with renal pelvic UUTUC (0 out of 76, p<0.0001). HER2-positive UUTUC showed a shorter recurrence time in the residual urinary bladder after nephroureterectomy with Kaplan-Meier analysis (p=0.0284) and multivariate analysis (p=0.0034). The results suggest that HER2 positivity in UUTUC is an independent predictive marker for early recurrence of urothelial carcinoma in the residual urinary bladder after surgery.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Yokohama City University Yokohama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsusaka
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Yokohama City University Yokohama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016009:Chi-Square Distribution; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014571:Urologic Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000737:chemistry* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: DISH; HER2; immunohistochemistry; tissue microarray; upper urinary tract; urothelial carcinoma