title: Congenital phimosis in patients with and without lichen sclerosus: distinct expression patterns of tissue remodeling associated genes.
abstract: OBJECTIVE
  Lichen sclerosus is a potentially important factor in the ongoing debate concerning the pathology of persistent congenital phimosis. We assessed the molecular differences of congenital phimosis in boys with and without lichen sclerosus compared to age matched boys with fully retractable foreskins to gain more insight into the pathogenesis of fibrotic remodeling of the prepuce.
  
  
  METHODS
  A total of 150 boys were circumcised in a prospective study between 2007 and 2009. Using target gene specific preamplification and quantitative real-time polymerase chain reaction based low density arrays, we measured the mRNA expression of 45 tissue remodeling associated genes in foreskins of boys with absolute phimosis and lichen sclerosus (8 patients) and those of an age matched group of boys with phimosis but no lichen sclerosus (8), as well as a control group with foreskins without delimitable changes (6). Complementary protein expression and inflammatory infiltrates were assessed by immunohistochemical analysis.
  
  
  RESULTS
  Cellular composition, inflammatory infiltrate and microenvironment as seen in histologically proven lichen sclerosis differed significantly from the other groups. In particular, lichen sclerosis was characterized by over expression of bone morphogenetic protein 2 and its corresponding receptor, matrix metalloproteinases 1 and 9 and tissue inhibitor of metalloproteinases 1, cytokine chemokine ligands 5 (RANTES) and interleukin 4, and transforming growth factor-β2 and its corresponding receptor. There were no major molecular differences between specimens from boys with congenital phimosis without signs of lichen sclerosis and controls.
  
  
  CONCLUSIONS
  Distinct expression patterns of tissue remodeling associated genes are evident in boys with congenital phimosis and lichen sclerosis, while congenital phimosis without lichen sclerosis represents a physiological condition.
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Pilatz
authors.forename: Bora
authors.initials: B
authors.lastname: Altinkilic
authors.forename: Eileen
authors.initials: E
authors.lastname: Schormann
authors.forename: Lavinia
authors.initials: L
authors.lastname: Maegel
authors.forename: Nicole
authors.initials: N
authors.lastname: Izykowski
authors.forename: Jan
authors.initials: J
authors.lastname: Becker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weidner
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
mesh_terms: D002648:Child; D002675:Child, Preschool; D052816:Foreskin / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D018459:Lichen Sclerosus et Atrophicus / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008297:Male; D010688:Phimosis / Q000150:complications / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies