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Association of TSC1/hamartin, 14-3-3sigma, and p27 expression with tumor outcomes in patients with pTa/pT1 urothelial bladder carcinoma

Alvarez, Victor
Fischer, Gabor
Beck, Amy
Published in American Journal of Clinical Pathology. 2008, vol. 129, no. 6, p. 918-923
Abstract 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.
Keywords 14-3-3 ProteinsAdultAgedAged, 80 and overCarcinoma, Transitional Cell/*genetics/metabolism/pathologyCyclin-Dependent Kinase Inhibitor p27/*genetics/metabolismDNA, Neoplasm/analysisExonucleases/*genetics/metabolismFemale*Gene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm Proteins/*genetics/metabolismNeoplasm Recurrence, LocalRetrospective StudiesTissue Array AnalysisTumor Markers, Biological/*genetics/metabolismTumor Suppressor Proteins/*genetics/metabolismUrinary Bladder Neoplasms/*genetics/metabolism/pathologyUrothelium/metabolism/pathology
PMID: 18480009
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Other version: http://ajcp.ascpjournals.org/content/129/6/918.full.pdf
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MHAWECH-FAUCEGLIA, Paulette et al. Association of TSC1/hamartin, 14-3-3sigma, and p27 expression with tumor outcomes in patients with pTa/pT1 urothelial bladder carcinoma. In: American Journal of Clinical Pathology, 2008, vol. 129, n° 6, p. 918-923. https://archive-ouverte.unige.ch/unige:19028

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Deposited on : 2012-03-27

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