title: Evaluation of combined h-TERT, bcl-2, and caspases 3 and 8 expression in cutaneous malignant melanoma based on tissue microarrays and computerized image analysis.
abstract: OBJECTIVE
  Deregulation of apoptotic pathways in cutaneous malignant melanoma appears to be correlated with chemoresistance and poor prognosis. Furthermore, telomerase (especially h-TERT) expression induces proliferation and also represents a potential target for vaccination regarding some types of malignancies.
  
  
  METHODS
  Using tissue microarrays (TMA) technology, 25 paraffin-embedded tissue samples of histologically confirmed malignant melanomas were cored at a diameter of 2 mm and re-embedded into one recipient block (final TMA density 24/25-96%). Immunohistochemistry (IHC) was performed by the use of anti-bcl-2, anti-caspase 3, anti-caspase 8 and anti- h-TERT antibodies. Protein expression levels were evaluated using a computerized image analysis system (CIA). SPSS (chi square test and inter-rater kappa) was used for statistical analysis.
  
  
  RESULTS
  Strong protein expression was observed in 1/24 (4.1%), 1/24 (4.1%), 2/24 (8.2%), and 4/24 (16.4%) cases regarding h-TERT, caspase 3, caspase 8 and bcl-2, respectively. Moderate was observed in 7/24 (29.1%), 8/24 (32.2%), 5/24 (20.2%), and 8/24(32.2%) cases, whereas reduced or absent expression demonstrated 16/24 (65%), 15/24 (60.2%), 17/24 (68.5%), and 12/24 (50 %) cases. Statistical significance was assessed correlating age to caspase 3 (p=0.05), Breslow's thickness to telomerase (p=0.013) and to bcl-2 (p=0.053), Clark's level to telomerase (p=0.008) and to bcl-2 (p=0.022), and finally ulceration to telomerase expression (p=0.007).
  
  
  CONCLUSIONS
  bcl-2 and telomerase expression are correlated to critical parameters of malignant melanoma, affecting its biological behavior. Furthermore, downregulation of proteins such as caspases 3/8, which normally induce apoptosis, is perhaps associated with resistance of the applied chemotherapeutic strategies in this type of malignancy.
authors: Lamia Institution of Technology, Lamia, Greece.
authors: P
authors: P
authors: Zygouris
authors: E
authors: E
authors: Tsiambas
authors: D
authors: D
authors: Tiniakos
authors: A
authors: A
authors: Karameris
authors: A E
authors: AE
authors: Athanassiou
authors: Ch
authors: Ch
authors: Kittas
authors: A
authors: A
authors: Kyroudi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D053181:Caspase 8 / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000473:pathology; D019098:Telomerase / Q000032:analysis / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D053181:Caspase 8