title: Immunolocalization of the tumor-sensitive calmodulin-like protein CALML3 in normal human skin and hyperproliferative skin disorders.
abstract: OBJECTIVE
  Calmodulin-like protein CALML3 is an epithelial-specific protein regulated during keratinocyte differentiation in vitro. CALML3 expression is downregulated in breast cancers and transformed cell lines making it an attractive marker for tumor formation. The objective of this study was to survey CALML3 localization in normal epidermis and in hyperproliferative skin diseases including actinic keratosis, squamous and basal cell carcinoma as well as verruca and psoriasis and to compare CALML3 immunoreactivity with the proliferation marker Ki-67.
  
  
  METHODS
  Paraffin-embedded tissue sections from normal human skin and hyperproliferative skin disorders were examined by immunohistochemistry and analyzed for localization and expression of CALML3 and Ki-67.
  
  
  RESULTS
  CALML3 was strongly expressed in differentiating layers of normal skin, staining the periphery in suprabasal cells and exhibiting nuclear localization in the stratum granulosum. CALML3 nuclear localization was inversely correlated to Ki-67 staining in each disease, indicating that CALML3 nuclear presence is related to terminal cell differentiation and postmitotic state.
  
  
  CONCLUSIONS
  Increased CALML3 expression in suprabasal layers is characteristic for differentiating keratinocytes in normal epidermis, and nuclear expression of CALML3 inversely correlates with expression of the proliferation marker Ki-67. This suggests that CALML3 is a useful marker for normal and benign hyperplastic epidermal development, whereas the loss of nuclear CALML3 indicates progression to a proliferative and potentially malignant phenotype.
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors: Richard D
authors: RD
authors: Bennett
authors: Mark R
authors: MR
authors: Pittelkow
authors: Emanuel E
authors: EE
authors: Strehler
mesh_terms: D002147:Calmodulin / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D014860:Warts / Q000378:metabolism
chemical_list: C082965:CALML3 protein, human; D002147:Calmodulin; D019394:Ki-67 Antigen
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