title: A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma.
abstract: BACKGROUND
  One third of patients with stage T1 urothelial carcinoma (UC) progress to muscle-invasive disease requiring radical surgery. Thus, reliable tools are needed for risk stratification of stage T1 UC.
  
  
  OBJECTIVE
  To investigate the extent to which stratification of stage T1 tumours into previously described molecular pathologic UC subtypes can provide improved information on tumour progression.
  
  
  METHODS
  A population-based cohort of 167 primary stage T1 UCs was characterised by immunohistochemistry and classified into the molecular subtypes urobasal (Uro, 32%), genomically unstable (GU, 58%), and squamous-cell-carcinoma-like (SCCL, 10%).
  
  
  METHODS
  Progression-free survival using univariate and multivariate models.
  
  
  CONCLUSIONS
  Subtype classification was validated using nine additional markers with known subtype-specific expression. Analysis of mRNA expression of progression biomarkers revealed a strong association with molecular subtype. Kaplan-Meier analyses showed that the risk of progression was low for Uro tumours and high for GU/SCCL tumours. High progression risk scores were found only for GU/SCCL tumours. Clinical risk factors such as multifocality, concomitant carcinoma in situ, invasion depth, lymphovascular invasion, and high CD3(+) lymphocyte infiltration were observed almost exclusively in GU/SCCL cases.
  
  
  CONCLUSIONS
  Molecular subtypes Uro, GU, and SCCL were identified in an independent population-based cohort of stage T1 UCs. Biomarkers and clinical risk factors for progression were associated with molecular subtype. Rapidly progressing T1 tumours were of subtype GU or SCCL and had either a high progression risk score or an elevated CD3(+) cell count.
  
  
  RESULTS
  We show that classification of stage T1 urothelial carcinoma into molecular subtypes can improve the identification of patients with progressing tumours.
authors.affiliation: Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden. Electronic address: oliver.patschan@med.lu.se.
authors.forename: Oliver
authors.initials: O
authors.lastname: Patschan
authors.affiliation: Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Gottfrid
authors.initials: G
authors.lastname: Sjödahl
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Chebil
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lövgren
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Lauss
authors.affiliation: Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Gudjonsson
authors.affiliation: Department of Urology, Helsingborg Hospital, Helsingborg, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Kollberg
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Aine
authors.affiliation: Tullgatan 1 B, Lund, Sweden.
authors.forename: Wiking
authors.initials: W
authors.lastname: Månsson
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
authors.affiliation: Department of Urology, Clinical Sciences Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Liedberg
authors.affiliation: Department of Oncology, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Höglund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D018570:Risk Assessment; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: Bladder cancer; High risk; Molecular classification; Outcome; Prognosis; Stage T1