title: MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone.
abstract: BACKGROUND
  The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis.
  
  
  METHODS
  MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA).
  
  
  RESULTS
  Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 were increased in the M1 patients as compared to M0 patients. Furthermore, a significant relationship was also highlighted between activin A concentration and the number of bone metastases and tumor grade, between MMP-9 and tumor grade, and between MMP-2 and CA15.3. ROC curve analysis showed a good diagnostic accuracy for activin A and CA15.3 but a poor accuracy for MMP-2 and MMP-9 in discriminating between M0 and M1 patients. However, CA15.3 retained the best diagnostic accuracy in this respect. In the PC group, only activin A and PSA levels were significantly increased in the M1 patients as compared to the M0 patients. A similar although not statistically significant trend was noted for MMP-9. Interestingly, a significant correlation was observed between PSA and activin A and MMP-9, and between Activin A and Gleason score and the number of skeletal metastases. ROC curve analysis showed a good diagnostic accuracy for activin A, MMP-9 and PSA and a poor diagnostic accuracy for MMP-2 in detecting M1 patients. However, PSA showed the highest diagnostic accuracy.
  
  
  CONCLUSIONS
  Activin A, MMP-2 and MMP-9 may be regarded as possible therapeutic targets in the treatment of metastatic bone disease. However, their usefulness as additional markers of bone metastasis remains to be better defined.
authors.affiliation: Section of Clinical Oncology, Policlinico Unversitario "Paolo Giaccone", 90127 Palermo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Incorvaia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Badalamenti
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Rini
authors.forename: Carlo
authors.initials: C
authors.lastname: Arcara
authors.forename: Salvatore
authors.initials: S
authors.lastname: Fricano
authors.forename: Carmela
authors.initials: C
authors.lastname: Sferrazza
authors.forename: Danilo
authors.initials: D
authors.lastname: Di Trapani
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Gaetano
authors.initials: G
authors.lastname: Leto
mesh_terms: D028341:Activins / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D018396:Mucin-1; C422405:activin A; D028341:Activins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9