title: Breslow density is a novel prognostic feature in cutaneous malignant melanoma.
abstract: OBJECTIVE
  In 1970, Breslow described his eponymously named thickness measurement. No-one has sought to enhance the Breslow thickness (BT). The aim of this study was to demonstrate a proof of concept that the density of melanoma cells at the position where the BT is measured is a morphological prognostic biomarker, which we name the Breslow density (BD). The hypothesis was that the BD has prognostic value for overall survival (OS) and is independent of the BT.
  
  
  RESULTS
  We analysed 100 cutaneous melanomas, and followed REMARK guidelines. The BD was the estimated percentage dermal area occupied by melanoma cells in a specified location. The BT and BD had a strong correlation (P = 2.1 × 10-11) but, despite this, they were independent prognostic factors for OS in Cox regression [BD hazard ratio (HR) 1.03, P = 0.001849; and BT HR 1.09, P = 0.000146]. This was corroborated by an independent effect on melanoma-specific survival. We assessed whether the BT and BD could be combined into a Breslow score. A prognostic index based on Cox regression coefficients was used, and this showed a marginal improvement in predicted 5-year survival as compared with the BT alone (area under the curve of 94.8% versus 96.7%).
  
  
  CONCLUSIONS
  We show a proof of concept that the BD represents a novel morphological prognostic biomarker that is independent of the BT, and that there is potential to combine these into a Breslow score. Larger studies are needed to validate the BD, but the simplicity of this biomarker makes it a strong candidate for translation to clinical practice.
authors: Department of Cellular Pathology, University Hospitals of Leicester, East Midlands Pathology Services (EMPATH), Leicester, UK.
authors: Hala
authors: H
authors: Rashed
authors: Department of Cancer Studies, University of Leicester, Leicester, UK.
authors: Katarina
authors: K
authors: Flatman
authors: Department of Cellular Pathology, University Hospitals of Leicester, East Midlands Pathology Services (EMPATH), Leicester, UK.
authors: Mark
authors: M
authors: Bamford
authors: Department of Cancer Studies, University of Leicester, Leicester, UK.
authors: Kah W
authors: KW
authors: Teo
authors: Department of Cellular Pathology, University Hospitals of Leicester, East Midlands Pathology Services (EMPATH), Leicester, UK.|Department of Cancer Studies, University of Leicester, Leicester, UK.
authors: Gerald
authors: G
authors: Saldanha
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
keywords: 
  REMARK
  ; biomarker; cancer; melanoma; prognosis; skin