Association of TSC1/hamartin, 14-3-3sigma, and p27 expression with tumor outcomes in patients with pTa/pT1 urothelial bladder carcinoma.
TSC1/hamartin is a tumor suppressor gene involved in the development of various malignancies, including bladder cancer. In vitro studies showed that hamartin controls cell proliferation partly by up-regulating p27 and 14-3-3sigma. This study was designed to explore the value of these biomarkers in predicting outcome in pTa/pT1 tumors and validate the regulation of p27 and 14-3-3sigma by hamartin in vivo using human bladder cancer tissue. A tissue microarray of 134 pTa and pT1 tumors was constructed, and sections were stained with hamartin, 14-3-3sigma, and p27 antibodies. In multiple Cox regression analysis, pTa/pT1 tumors with reduced or low expression of hamartin tended to have higher risk of progression (P = .030). High-grade tumors tended to be at higher risk of progression in comparison with low-grade tumors (P < .001). The combination of expression of these 3 biomarkers did not add predictive value regarding disease outcomes. Low hamartin expression and high tumor grade are independent factors in predicting faster pTa/pT1 tumor progression. In a subset of pTa/pT1 tumors, hamartin has a role in bladder carcinogenesis by positively regulating 14-3-3sigma and p27.
Mhawech-Fauceglia
Paulette
P
Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Alvarez
Victor
V
Fischer
Gabor
G
Beck
Amy
A
Herrmann
François R
FR
D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005092:Exonucleases / Q000235:genetics* / Q000378:metabolism; D005095:Exoribonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human