Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis.
OBJECTIVE
Despite a lack of consensus concerning the etiology of interstitial cystitis (IC) the loss of impermeability and other abnormalities of the urothelium are features of the disease. In this study the distribution of proteins involved with epithelial adhesion, cellular differentiation and bladder impermeability in urothelial biopsies were explored by the immunohistochemical assessment of E-cadherin, ZO-1, uroplakin and chondroitin sulfate.


METHODS
Biopsies obtained from 27 patients with IC and 7 controls were immediately fixed in formalin, immunohistochemically labeled for the described proteins and scored for protein expression, morphology and differentiation.


RESULTS
Only 3 IC samples appeared completely normal, while 24 of the 27 showed an abnormality in at least 1 marker and in 6 all 4 markers were abnormal. In patients vs controls findings were abnormal for uroplakin in 13 of 27 vs 1 of 7 (p = 0.085), for E-cadherin (over expressed) in 18 of 27 vs 0 of 7 (p = 0.0021), for ZO-1 in 11 of 27 vs 0 of 7 (p = 0.046) and for chondroitin sulfate in 15 of 27 vs 0 of 7 (p = 0.0054). The morphology/polarity score significantly correlated with ZO-1 (Pearson r = 0.3935, p = 0.0423) and chondroitin sulfate (Pearson r = 0.7079, p <0.0001) expression. Chondroitin sulfate and ZO-1 showed a high correlation with each other (Pearson r = 0.5587, p = 0.0025). Uroplakin and E-cadherin expression were independent of all other markers.


CONCLUSIONS
The findings reported strongly suggest abnormal differentiation in the IC bladder. The disruption of ZO-1 is similar to that reported in feline IC. Elevated E-cadherin may represent an adaptation to increased bladder permeability.
Slobodov
Gennady
G
Department of Urology, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Feloney
Michael
M
Gran
Christopher
C
Kyker
Kimberly D
KD
Hurst
Robert E
RE
Culkin
Daniel J
DJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis; D002809:Chondroitin Sulfates / Q000032:analysis / Q000096:biosynthesis; D018856:Cystitis, Interstitial / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D060170:Uroplakin II; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D015820:Cadherins; D008565:Membrane Proteins; C554658:UPK2 protein, human; D060170:Uroplakin II; D002809:Chondroitin Sulfates