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9

19–22 APRIL, 2017, BARCELONA, SPAIN

13:42–13:45

S1-5 (PP)

FGF8/10/2R IN HUMAN HYPOSPADIAS FORESKIN:

DOES THEIR EXPRESSION PATTERN DIFFER FROM

NORMAL FORESKIN?

Bernhard HAID

1

, Felix NÄGELE

2

, Elisabeth PECHRIGGL

2

and Josef OSWALD

3

1) Hospital of the Sisters of Charity, Pediatric Urology, Linz, AUSTRIA - 2) Medical University Innsbruck, Clinical and

Functional Anatomy, Innsbruck, AUSTRIA - 3) Hospital of the Sisters of Charity, Department of Pedatric Urology, Linz,

AUSTRIA

PURPOSE

The fibroblast growth factor (FGF) pathway plays a major role in the development of the urethra and

the penis, affecting the urethra as well as developing penile epithelia by mesenchymal signaling.

In murine models, the lack of involved signal molecules or receptors has repeatedly been shown

to lead to the development of hypospadias. We aimed at investigating whether in human tissue

samples aberrant expression of FGF8/10/R2 in skin is present and corresponds to hypospadias

severity as compared to normal foreskin.

MATERIAL AND METHODS

Foreskin samples from 21 patients with hypospadias (11 distal and 10 proximal) and 10 patients

with normally developed genitalia were harvested during surgery. Immunohistochemistry (IHC)

using antibodies against FGF8, FGF10 and FGFR2 was performed under standardized conditions

(Ventana

®

, Roche). Staining localization and distribution of positive cells in the epithelial layer

(basal, partly, full) and the stroma (no stromal positive cells, few, aggregates) were categorized.

RESULTS

Patients with hypospadias consistently showed an aberrant expression pattern for FGF8/10/2R

(p<0.0001 for all markers). Stromal positive cells were present more often (p<0.0001) in hypospa-

dias samples compared to normal skin, partly aggregating (57.14% of hypospadias, never in normal

skin). The epithelial expression patterns correlated with meatal localization, showing a significant

difference between distal and proximal hypospadias (p=0.047). Conversely, the distribution of

stromal positive cells or their aggregation was not related to meatal localization (p=0.405).

CONCLUSIONS

We noted important differences between localization and distribution of FGF8, FGF10 and FGF2R

comparing normal foreskin to foreskin of hypospadias patients. This finding supports the hypothesis

of mesothelial-epithelial interaction and corresponds probably with the clinical estimation of “dys-

plastic” skin.