title: Enhanced FHL2 and TGF-β1 Expression Is Associated With Invasive Growth and Poor Survival in Malignant Melanomas.
abstract: OBJECTIVE
  This study examines the expression and the role of four-and-a-half LIM domains protein 2 (FHL2) and transforming growth factor β1 (TGF-β1) in human malignant melanoma. It is determined whether both proteins influence melanoma survival time.
  
  
  METHODS
  We analyzed the immunohistochemical staining intensities of FHL2 and TGF-β1 in normal skin and in 50 malignant melanomas with different mutation status (BRAF-V600E, NRAS codon 61 mutation, and wild type). Survival data were available for 45 cases.
  
  
  RESULTS
  In melanocytes of nonneoplastic human skin, FHL2 expression was absent. In contrast, 38 (76%) of 50 melanomas showed strong cytoplasmic and partly nuclear FHL2 expression. At the invasion front, cytoplasmic TGF-β1 staining was observed in 32 (64%) of 50 melanomas, and a correlation of FHL2 and TGF-β1 staining intensities was detectable. In follow-up analyses, enhanced FHL2 and TGF-β1 staining intensities in the tumor invasion front were associated with poor survival.
  
  
  CONCLUSIONS
  Enhanced FHL2 and TGF-β1 expression is correlated with poor survival in human malignant melanoma. Protumorigenic effects of autocrine TGF-β1 secretion might be exerted by induction of FHL2 expression in melanoma cells. Since melanomas treated with targeted therapies often do not show sufficient response rates, inhibition of FHL2 and/or TGF-β1 might be a promising therapeutic approach.
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany;
authors.forename: Philipp
authors.initials: P
authors.lastname: Westphal
authors.affiliation: Department of Dermatology, University Hospital of Cologne, Cologne, Germany; and.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Florin
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany;
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Czerwitzki
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany;
authors.forename: Nina
authors.initials: N
authors.lastname: Olligschläger
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany;
authors.forename: Claudia
authors.initials: C
authors.lastname: Wodtke
authors.affiliation: Center for Clinical Research, University of Freiburg Medical School, Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany;
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: From the Institute of Pathology, University of Cologne Medical School, Cologne, Germany; nicolaus.friedrichs@uk-koeln.de.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Friedrichs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D060850:LIM-Homeodomain Proteins / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C105987:FHL2 protein, human; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1
keywords: FHL2; Invasion; Melanoma; Survival; TGF-β1