title: Differential diagnosis of bladder versus colorectal adenocarcinoma: keratin 7 and GATA3 positivity in nuclear ß-catenin-negative glandular tumours defines adenocarcinoma of the bladder.
abstract: OBJECTIVE
  This study evaluates immunohistochemical markers for the differential diagnosis of primary bladder adenocarcinoma (BAC) from secondarily involving colorectal adenocarcinoma (CAC). Additional staining of putative precursor lesions (cystitis cystica et glandularis (CC) and intestinal metaplasia (IM)) supports insights into metaplastic cell development and aberrant differentiation in tumours.
  
  
  METHODS
  Tissue microarray sections of formalin-fixed, paraffin-embedded tissues from clinically verified 11 BAC, 11 CAC, 18 invasive urothelial carcinomas (UCs), 22 normal urothelium samples, 25 CC and 15 IM were stained for keratin 7, 5/6, 5/14 and 20, ß-catenin, e-cadherin, cadherin 17, cdx2, uroplakin II and III, CD10, androgen receptor (AR), S100P, MUC2, MUC5AC and GATA3 expression. Data were analysed using Kruskal-Wallis/Dunn's multiple comparison test and Fisher's exact test.
  
  
  RESULTS
  Significant difference (p<0.05) between all three tumour groups was observed for keratin 7 only. Further significant difference between BAC and CAC was found for GATA3 and nuclear ß-catenin staining. BAC-positive/CAC-negative markers without significance were: p63, keratin 5/6, 5/14, uroplakins II/III and AR. CC showed a urothelial phenotype (p63+, GATA3+, S100P+, uroplakin+ in single cells) with initial signs of intestinal differentiation (single cells cdx2+ or cadherin 17+). IM displayed a full intestinal phenotype (p63-, all urothelial markers-, cdx2/MUC2/MUC5AC+, cadherin17+).
  
  
  CONCLUSIONS
  Differential diagnosis of BAC and CAC remains difficult, but positive staining for keratin 7 in nuclear ß-catenin-negative tumours argues for BAC. Additional markers like GATA3 and p63 may be added, as positivity in some cases may be helpful. However, for reliable histological diagnosis, knowledge of comprehensive clinical data is still essential.
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Broede
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Oll
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Maurer
authors.affiliation: Institute of Pathology, Munich-North, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Siegert
authors.affiliation: Institute of Pathology, HELIOS Clinic Wuppertal, Wuppertal, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stoerkel
authors.affiliation: Institute of Pathology, HELIOS Clinic Wuppertal, Wuppertal, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Golz
authors.affiliation: Institute of Pathology, Technical University Munich, Munich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Schwamborn
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Veeck
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Nadine T
authors.initials: NT
authors.lastname: Gaisa
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D003937:Diagnosis, Differential; D050990:GATA3 Transcription Factor / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7 / Q000096:biosynthesis; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000556:secondary; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C507497:KRT7 protein, human; D053552:Keratin-7; D051176:beta Catenin
keywords: URINARY TRACT TUMOURS; UROGENITAL PATHOLOGY; UROPATHOLOGY