IIICS de novo glycosylated fibronectin as a marker for invasiveness in urothelial carcinoma of the urinary bladder (UBC).
OBJECTIVE
The urothelial carcinoma is the most frequent malignancy of the urinary bladder (UBC). The transition into invasive growth is accompanied by several histological changes including an oncofoetal reorganization of the extracellular matrix. Recently, the occurrence of oncofoetal fibronectin with an O-linked glycosylation in the IIICS region (oncf Fn) was shown to be present in urine from UBC patients and was recommended as a tumour marker. Until now there are no data available regarding the source and distribution of oncf Fn in UBC and its value for the assessment of invasiveness.


METHODS
oncf Fn was analysed in noninvasive and invasive UBC using immunohistochemistry and western blot. Additionally, the mRNA expression of the IIICS splicing region was evaluated by quantitative real time RT-PCR.


RESULTS
Immunohistochemical results reveal a highly significant correlation of oncf Fn to invasiveness. Papillary tumours regularly show no positivity. In western blot, invasive UBC show a strongly increased amount of the 250 kDa oncf Fn. Additionally, several smaller bands could be shown suggesting a proteolytic processing of Fn. The mRNA of the IIICS region shows a 21.5-fold increase in invasive UBC compared with noninvasive carcinomas.


CONCLUSIONS
In summary, immunohistochemistry of oncf Fn is a valuable histological marker for invasiveness of urothelial carcinoma of the urinary bladder. The restricted and invasion-associated tissue distribution of immunoreactivity enables to monitor the recurrence of invasive UBC by a quantitative evaluation of IIICS O-linked glycosylated Fn in urine.
Richter
Petra
P
Institute of Pathology, Friedrich Schiller University, Jena, Germany.
Junker
Kerstin
K
Franz
Marcus
M
Berndt
Angela
A
Geyer
Christiane
C
Gajda
Mieczyslaw
M
Kosmehl
Hartwig
H
Berndt
Alexander
A
Wunderlich
Heiko
H
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis*; D017127:Glycation End Products, Advanced; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D000093844:Glycated Proteins
D014408:Biomarkers, Tumor; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D020033:Protein Isoforms; D012333:RNA, Messenger; C045099:glycated fibronectin; D000093844:Glycated Proteins; C121542:oncofetal fibronectin