title: Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy.
abstract: Purpose of this study was to evaluate prognostic impact of rare variants of urothelial bladder cancer (BC) after treatment with combined radiochemotherapy (RCT). To this end tumour tissue of 238 patients with urothelial carcinoma (UC) treated with transurethral resection of the bladder (TUR-B) and RCT with curative intent was collected. Histomorphological analysis included re-evaluation and semi-quantitative assessment of rare UC subtypes. Additionally, human epidermal growth factor receptor 2 (HER2) chromogenic in situ hybridisation (CISH) was performed in tumours with a micropapillary component exceeding 30 %. Long-term follow-up was available for 200 patients (range 3-282 months). Variant UC histology was found in 45 of 238 tumours, most frequently micropapillary UC (N = 17) including cases with a small fraction of tumour with micropapillary morphology. The mere presence of micropapillary morphology did not affect prognosis. In tumours with extensive (≥30 %) micropapillary morphology (N = 8) Kaplan-Meier analysis revealed significantly worse cancer specific survival (CSS) (P = 0.002) compared to conventional UC (mean survival times 97 months and 229 months, respectively). Univariate Cox regression analysis of cases with ≥30 % micropapillary morphology revealed a hazard ratio of 4.726 (95 % CI 1.629-13.714) for CSS (P = 0.004). CISH revealed HER2 gene amplification in 3/10 tumours with ≥30 % micropapillary component. In conclusion, for BC treated with TUR-B and RCT, the presence of micropapillary morphology in more than 30 % of the tumour is an adverse prognostic factor. Further studies are needed to evaluate a potential benefit of different, especially multimodal treatment strategies for micropapillary UC and also other subtypes of UC. Her2 represents a promising therapeutic target in a subset of micropapillary UC.
authors.affiliation: Department of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Germany. Simone.Bertz@uk-erlangen.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Bertz
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wach
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Taubert
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Merten
authors.affiliation: Department of Urology, AKH - General Hospital, Medical Faculty, Johannes Kepler University Linz, Linz, Austria.
authors.forename: F S
authors.initials: FS
authors.lastname: Krause
authors.affiliation: Clinical Cancer Registry, Tumor Center of the University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schick
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: O J
authors.initials: OJ
authors.lastname: Ott
authors.affiliation: Department of Pathology, City Hospital Fürth, Fürth, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Weigert
authors.affiliation: Department of Pathology, City Hospital Fürth, Fürth, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Dworak
authors.affiliation: Department of Radiation Therapy and Oncology, University of Frankfurt am Main, Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rödel
authors.affiliation: Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wullich
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Keck
authors.affiliation: Department of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Krankenhausstraße 8-10, 91054, Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000473:pathology*; D059248:Chemoradiotherapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D019459:Urothelium / Q000473:pathology
keywords: HER2; Micropapillary; Radiochemotherapy; Rare variants; Urothelial carcinoma