Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease.
OBJECTIVE
To determine whether COX-2, bcl-2 and neoangiogenesis are related to human prostate cancer relapse after definitive surgical treatment and progression toward androgen independence and to evaluate the association between the patterns of these tumoral biomarkers and other standard clinico-pathological parameters (such as Gleason score, PSA, TNM stage).


METHODS
We retrospectively analyzed the records on 126 prostate cancer samples from patients treated at our University Hospital from 1995 to 2002. The 72 patients with clinically localized disease (group 1) had undergone radical prostatectomy. Another 54 patients (group 2) had metastatic androgen-independent disease. Archived material relating to the subjects was then immunostained for bcl-2, COX-2 and CD-31, using an anti-bcl-2 monoclonal primary antibody, an anti-COX-2 polyclonal rabbit antibody and an anti-CD-31 monoclonal mouse antibody to evaluate neoangiogenesis (MVD, microvessel density).


RESULTS
We found that bcl-2, COX-2 and MVD expression increased from group 1 to group 2. The intergroup difference was significant only for high MVD (P < 0.05). On the other hand, high MVD, high bcl-2 and high COX-2 expression was correlated with a higher PSA level (P < 0.01), whereas only a high MVD was also related with Gleason score (P < 0.05). We used univariate analysis to evaluate the prognostic impact of biologic and clinico-pathologic parameters on the disease-free-survival of 72 patients treated by radical prostatectomy. A total of 30 patients (41.6%) experienced biochemical relapse; bcl-2, COX-2 and MVD significantly correlated with disease relapse in these patients. In fact, we observed disease relapse in 24/45 (53%) with high bcl-2 expression, in 15/21 (71%) with a high MVD count and finally, in 30/58 (52%) with high COX-2 expression. Finally, PSA value and Gleason score were the only two biologic markers significantly associated to disease relapse in a multivariate analysis.


CONCLUSIONS
Our results strongly support a role for bcl-2, COX-2 and angiogenesis in the development and progression of prostate cancer. Of course, we are aware of the small sample size considered in our study. Further investigations would better clarify the prognostic and therapeutic implications of these findings.
Di Lorenzo
G
G
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università degli Studi di Napoli Federico II, Naples, Italy. giuseppedilorenzoncol@hotmail.com
De Placido
S
S
Autorino
R
R
De Laurentiis
M
M
Mignogna
C
C
D'Armiento
M
M
Tortora
G
G
De Rosa
G
G
D'Armiento
M
M
De Sio
M
M
Bianco
A R
AR
D'Armiento
F P
FP
D051546:Cyclooxygenase 2; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012189:Retrospective Studies
D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D017430:Prostate-Specific Antigen