Adhesion molecules alpha, beta and gamma-catenin as prognostic factors of tumour progression in upper urinary tract urothelial tumours: the role of AKT-P/GSK-3beta/beta-catenin pathway.
OBJECTIVES To evaluate alpha, beta and gamma-catenin expression in upper urinary tract urothelial tumours (UUTC) and determine their value as prognostic factors; to investigate the correlation between the catenin complex and the AKT pathway. PATIENTS AND METHODS We retrospectively analysed 114 consecutive patients treated at our institution from 1990 to 2004; the mean follow-up was 54 months. Tumour samples were available from 70 patients, and included in tissue microarrays for immunohistochemical analysis. The antibodies used were anti-alpha, -beta and gamma-catenin, and antiphospho-AKT. The prognostic value of the expression of these molecules was analysed using tumour progression and cancer-specific survival as end-points. RESULTS Of the 114 patients, 27% developed tumour progression; the cancer-specific and overall survival were 77% and 60.6%, respectively. Abnormal alpha, beta and gamma-catenin expression was found in 44 (63%), 22 (31%) and 28 (41%) patients, respectively; the abnormal catenin expression patterns correlated with each other. Positive cytoplasm phospho-AKT expression was found in 27 (39%) patients. Three of them were found to have cytoplasmic beta-catenin accumulation and none of them nuclear expression. beta-catenin expression was the only one that was an independent marker of tumour progression, with a hazard ratio (95% confidence interval) of 3.1(1.2-8.6), together with grade (7.1, 1.2-55.8) and stage (4.6, 2.1-10). In the cancer-specific survival analysis, again beta-catenin was an independent prognostic factor (3.4, 1-11.5) together with stage (4.6, 2.2-9.8). CONCLUSIONS The loss of the normal membrane beta-catenin expression constitutes an independent factor of tumour progression and cancer-specific survival. Our data suggest that the AKT/GSK3beta/beta-catenin signalling pathway is not activated in the UUTC carcinogenesis.
Izquierdo
Laura
L
Department of Urology, Hospital Clinic, Barcelona, Spain. laurizquierdo@hotmail.com
Truan
David
D
Petit
Anna
A
Gutiérrez
Rafael
R
Mallofré
Carme
C
Alcaraz
Antonio
A
D000368:Aged; D000369:Aged, 80 and over; D051177:Catenins / Q000378:metabolism*; D018450:Disease Progression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000378:metabolism
D051177:Catenins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3