Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression in localized human prostatic adenocarcinoma as predictors of clinical outcome: a clinicopathological and immunohistochemical study of 43 cases.
OBJECTIVE
Skeletal metastases are the hallmark of advanced prostate cancer and recurrence after local surgery is common. Currently to our knowledge no biological markers predict the risk of disease progression in individuals with localized prostate cancer. In a search for predictive markers we evaluated the expression of bone sialoprotein and bone morphogenetic protein 6, 2 bone related proteins, and the angiogenic factor thymidine phosphorylase.


METHODS
The study population included 43 men who presented with localized prostate cancer treated with radical prostatectomy. Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression was assessed by immunohistochemical testing. Results were analyzed in relation to pathological disease stage, Gleason score and clinical outcome. Clinical followup was 4.3 to 11.4 years after surgery (median 7.9).


RESULTS
Disease did not progress in 17 of the 43 cases, while recurrence and/or metastasis developed in the other 26 at a median of 6.5 and 6.9 years, respectively. Bone sialoprotein and bone morphogenetic protein 6 expression detected in 28 (65%) and 29 (67%) of the 43 samples, respectively, was significantly associated (p = 0.0001). Thymidine phosphorylase detected in 26 samples (60%) was not related to bone sialoprotein and/or bone morphogenetic protein 6 positivity. Bone sialoprotein and/or bone morphogenetic protein 6 expression correlated with bone metastasis, while thymidine phosphorylase expression was related to local recurrence (p = 0.002 and/or 0.007, and 0.00007, respectively). On multivariate analysis only the correlation of thymidine phosphorylase expression with recurrence remained statistically significant (p = 0.002). Co-expression of the 3 markers was observed in the samples of 10 of the 11 patients (90%) with bone metastases and only in 5 of the 17 (29%) who were disease-free.


CONCLUSIONS
This study indicates that the expression of bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase determined at a clinically early stage of disease by a simple immunohistochemical technique would enable subgroups of patients to be identified that are at different risks of bone metastasis or recurrence. Detection of such markers would provide additional prognostic information that would be useful for patients with intermediate or low Gleason score or stage disease. These patients would benefit from a more adapted clinical follow-up.
De Pinieux
G
G
Laboratoire de Cytogénétique moléculaire et Oncologie, CNRS-Institut Curie, Departement de Biostatistiques, Institut Curie, CHU Cochin, Université Paris V, Paris Cedex, France.
Flam
T
T
Zerbib
M
M
Taupin
P
P
Bellahcène
A
A
Waltregny
D
D
Vieillefond
A
A
Poupon
M F
MF
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001859:Bone Neoplasms / Q000556:secondary; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016896:Treatment Outcome
C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D013939:Thymidine Phosphorylase