title: Immunohistochemically detectable bcl-2 expression in metastatic melanoma: association with survival and treatment response.
abstract: OBJECTIVE
  The antiapoptotic protein Bcl-2 is supposed to influence the treatment responsiveness of different malignancies. In the present study the prognostic and predictive significance of Bcl-2 expression for survival and response to an administered therapy was explored in patients with metastatic melanoma. Also, the correlation between Bcl-2 expression and proliferation activity of tumor cells was defined to examine the regulatory role of Bcl-2 in proliferation.
  
  
  METHODS
  Sixty metastatic melanomas obtained from patients treated with chemoimmunotherapy were examined by immunohistochemistry with anti-Bcl-2 and anti-Ki-67 (MIB-1) antibodies. Proliferation activity was expressed in percentages as MIB-1 index.
  
  
  RESULTS
  The presence of Bcl-2 immunoreactivity was associated with a significantly lower MIB-1 index (p = 0.016), and a longer disease-free survival (p = 0.004). The lack of Bcl-2 expression was related to a higher response rate to therapy in comparison to a diffuse and focal pattern of Bcl-2 expression (p = 0.017). Although the presence of Bcl-2 immunoreactivity as such did not correlate with survival after the initiation of chemoimmunotherapy, the focal Bcl-2 expression pattern was strongly associated with a worse prognosis compared to a diffuse expression or a lack of Bcl-2 staining (p < 0.0001).
  
  
  CONCLUSIONS
  Our results support the role of Bcl-2 in the regulation of cell proliferation and suggest that an increase of metastatic potential and progression of malignant melanoma is associated with a loss of Bcl-2 expression. The lack of Bcl-2 expression could be a predictor of the response to chemoimmunotherapy, whereas the Bcl-2 expression pattern, possibly indicating the heterogeneity of the tumors, might be a potential prognostic factor for survival after the initiation of therapy.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Central Hospital, Finland.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Vlaykova
authors.forename: Lauri
authors.initials: L
authors.lastname: Talve
authors.forename: Marjo
authors.initials: M
authors.lastname: Hahka-Kemppinen
authors.forename: Micaela
authors.initials: M
authors.lastname: Hernberg
authors.forename: Timo
authors.initials: T
authors.lastname: Muhonen
authors.forename: Yrjö
authors.initials: Y
authors.lastname: Collan
authors.forename: Seppo
authors.initials: S
authors.lastname: Pyrhönen
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D019394:Ki-67 Antigen; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2