Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications.
BACKGROUND
Wnt-1 and beta-catenin expression levels play an important role in several malignancies. The authors determined the level of production of Wnt-1 and beta-catenin in normal and malignant human prostate carcinoma cell lines. Surgical pathology specimens from primary prostatic adenocarcinoma, lymph node metastases, and skeletal metastases were used to establish a correlation between the level of Wnt-1/beta-catenin expression, Gleason score, serum prostate-specific antigen (PSA) status, and androgen receptor (AR) status.


METHODS
Immunohistochemical analysis was used to investigate the expression of Wnt-1 and beta-catenin in human prostate carcinoma cell lines and in paraffin embedded sections of archival samples from 67 patients with prostate carcinoma. Comparison was made with the expression of tumoral AR and lymph node and skeletal metastases. These results were used to establish a correlation with the clinicopathologic status of patients with prostate carcinoma.


RESULTS
Levels of both Wnt-1 and beta-catenin were low in normal prostate cells and were expressed highly in human prostate carcinoma cell lines. Wnt-1 and cytoplasmic/nuclear beta-catenin expression was observed in 52% and 34%, respectively, of primary prostate carcinoma specimens. High levels of expression of Wnt-1 and beta-catenin were seen in 77% of lymph node metastases and in 85% of skeletal metastases. These increased levels of expression were related directly to the Gleason score and to serum PSA levels in these patients. Maximum levels of Wnt-1 and beta-catenin production were observed in skeletal metastases, whereas normal prostatic tissue failed to exhibit any detectable nuclear staining for beta-catenin.


CONCLUSIONS
High levels of Wnt-1 and beta-catenin expression were associated with advanced, metastatic, hormone-refractory prostate carcinoma, in which they can serve as markers of disease progression.
Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
Gaoping
G
Chen
Nicholas
N
Shukeir
Anil
A
Potti
Kanishka
K
Sircar
Armen
A
Aprikian
David
D
Goltzman
Shafaat A
SA
Rabbani
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000728:Androgens / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D011379:Prognosis; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin
D000728:Androgens; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin; D017430:Prostate-Specific Antigen