title: Protein markers of malignant potential in penile and vulvar lichen sclerosus.
abstract: OBJECTIVE
  Lichen sclerosus is an inflammatory skin disorder affecting anogenital areas in males and females that is associated with squamous cell carcinoma. However, there is a lack of data on the role of biomarkers for predicting lichen sclerosus progression to squamous cell carcinoma. We focused on early protein markers of squamous cell carcinoma and their expression in lichen sclerosus to improve the mechanistic and diagnostic understanding of lichen sclerosus.
  
  
  METHODS
  We performed an extensive PubMed® and MEDLINE® search for protein markers found in early stages of vulvar and penile squamous cell carcinoma, and their prevalence in associated lichen sclerosus lesions.
  
  
  RESULTS
  In recent years several markers have been implicated as precursor markers for malignant transformation of lichen sclerosus into squamous cell carcinoma, including p53, Ki-67, γ-H2AX, MCM3 and cyclin D1. These proteins are up-regulated in lichen sclerosus of the vulva/penis and squamous cell carcinoma. Various levels of evidence show an association between lichen sclerosus and squamous cell carcinoma. p16 is over expressed in penile and vulvar squamous cell carcinoma associated with human papillomavirus infection but conflicting reports exist about its expression in lichen sclerosus. The angiogenesis markers vascular endothelial growth factor and cyclooxygenase-2 are expressed at higher levels, and microvessel density is increased in vulvar lichen sclerosus and squamous cell carcinoma, indicating a possible similar association in penile lichen sclerosus.
  
  
  CONCLUSIONS
  Only a minority of lichen sclerosus cases are associated with squamous cell carcinoma. However, the therapeutic implications of a squamous cell carcinoma diagnosis are severe. Clinically, we lack an understanding of how to separate indolent lichen sclerosus cases from those in danger of progression to squamous cell carcinoma. Several protein markers show promise for further delineating the pathobiology of lichen sclerosus and the potential malignant transformation into squamous cell carcinoma.
authors: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Bayard C
authors: BC
authors: Carlson
authors: Matthias D
authors: MD
authors: Hofer
authors: Nathaniel
authors: N
authors: Ballek
authors: Ximing J
authors: XJ
authors: Yang
authors: Joshua J
authors: JJ
authors: Meeks
authors: Chris M
authors: CM
authors: Gonzalez
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005260:Female; D006801:Humans; D018459:Lichen Sclerosus et Atrophicus / Q000473:pathology*; D008297:Male; D010412:Penile Neoplasms / Q000473:pathology*; D007724:Vulvar Lichen Sclerosus / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: COX-2; HA; HG-VIN; HPV; ISCC; LS; MCM; MVD; PeIN; SCC; VEGF; VIN; carcinoma, squamous cell; cell transformation, neoplastic; cyclooxygenase 2; d-VIN; differentiated VIN; high grade VIN; human papillomavirus; hyaluronan; invasive vulvar SCC; lichen sclerosus; lichen sclerosus et atrophicus; microvessel density; minichromosome maintenance; pRb; penile intraepithelial neoplasia; penis; phosphorylated retinoblastoma protein; squamous cell carcinoma; vascular endothelial growth factor; vulva; vulvar intraepithelial neoplasia