title: Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder.
abstract: OBJECTIVE
  Through alternative splicing of the extracellular matrix protein tenascin-C (Tn-C) primary transcript nine type III homology repeats can be independently included or omitted. Large, low spliced Tn-C variants (Tn-C(L)) are preferentially expressed during tissue remodelling processes like tumour invasion to modulate cell migration. The study was aimed to evaluate the differential expression of Tn-C splicing domains in urinary bladder carcinoma with respect to the invasive behaviour.
  
  
  METHODS
  The deposition and synthesis of the Tn-C splicing domains A1-D was analysed in 34 urinary bladder carcinomas by semiquantitative immunohistochemistry using domain specific antibodies and by RT-PCR. Results were correlated to tumour stage and grade.
  
  
  RESULTS
  There is a significant increase of Tn-C(L) with higher tumour stage and grade. Immunohistochemistry revealed a more restricted distribution pattern of A1, B, and/or D domain containing Tn-C variants to invasive tumours, tumour vessels, and to destructed muscle. The mRNA expression patterns of the domains A1-A3 are similar among the different carcinomas. Stronger differences exist in the region from the B to D domain. In general, the domains AD1/C are rarely expressed. AD1 domain expression seems to be connected with compact invasion pattern.
  
  
  CONCLUSIONS
  In urinary bladder carcinoma a differential expression of Tn-C splicing variants exists in dependence of tumour type, vascularization, and invasive behaviour. Therefore, the detection of different Tn-C splicing domains could be useful for assessment of muscle invasion, tumour surveillance, as well as target structures for antibody based tumour detection and therapy.
authors.affiliation: Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740, Jena, Germany. Alexander.Berndt@med.uni-jena.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
authors.forename: Katharina
authors.initials: K
authors.lastname: Anger
authors.forename: Petra
authors.initials: P
authors.lastname: Richter
authors.forename: Laura
authors.initials: L
authors.lastname: Borsi
authors.forename: Simon
authors.initials: S
authors.lastname: Brack
authors.forename: Michela
authors.initials: M
authors.lastname: Silacci
authors.forename: Marcus
authors.initials: M
authors.lastname: Franz
authors.forename: Heiko
authors.initials: H
authors.lastname: Wunderlich
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Luciano
authors.initials: L
authors.lastname: Zardi
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Hartwig
authors.initials: H
authors.lastname: Kosmehl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000737:chemistry; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019154:Protein Splicing; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000032:analysis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology; D019459:Urothelium / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019063:Tenascin