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2. Gefitinib Inhibits the Growth and Invasion of Urothelial Carcinoma Cell Lines in which Akt and MAPK Activation Is Dependent on Constitutive Epidermal Growth Factor Receptor Activation

Author

Nicolle, Gaëlle, primary, Daher, Ahmad, additional, Maillé, Pascale, additional, Vermey, Marcel, additional, Loric, Sylvain, additional, Bakkar, Ashraf, additional, Wallerand, Hervé, additional, Vordos, Dimitrios, additional, Vacherot, Francis, additional, de Medina, Sixtina Gil Diez, additional, Abbou, Claude C., additional, Kwast, Theodore Van der, additional, Thiery, Jean-Paul, additional, Radvanyi, François, additional, and Chopin, Dominique K., additional

Published
2006
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3. Frequent FGFR3 Mutations in Papillary Non-Invasive Bladder (pTa) Tumors

Author

Billerey, Claude, primary, Chopin, Dominique, additional, Aubriot-Lorton, Marie-Hélène, additional, Ricol, David, additional, Gil Diez de Medina, Sixtina, additional, Van Rhijn, Bas, additional, Bralet, Marie-Pierre, additional, Lefrere-Belda, Marie-Aude, additional, Lahaye, Jean-Baptiste, additional, Abbou, Claude C., additional, Bonaventure, Jacky, additional, Zafrani, Elie Serge, additional, van der Kwast, Theo, additional, Thiery, Jean Paul, additional, and Radvanyi, Francois, additional

Published
2001
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4. Frequent FGFR3Mutations in Papillary Non-Invasive Bladder (pTa) Tumors

Author

Billerey, Claude, Chopin, Dominique, Aubriot-Lorton, Marie-Hélène, Ricol, David, Gil Diez de Medina, Sixtina, Van Rhijn, Bas, Bralet, Marie-Pierre, Lefrere-Belda, Marie-Aude, Lahaye, Jean-Baptiste, Abbou, Claude C., Bonaventure, Jacky, Zafrani, Elie Serge, van der Kwast, Theo, Thiery, Jean Paul, and Radvanyi, Francois

Abstract

We recently identified activating mutations of fibroblast growth factor receptor 3 (FGFR3) in bladder carcinoma. In this study we assessed the incidence of FGFR3mutations in a series of 132 bladder carcinomas: 20 carcinoma in situ(CIS), 50 pTa, 19 pT1, and 43 pT2–4. All 48 mutations identified were identical to the germinal activating mutations that cause thanatophoric dysplasia, a lethal form of dwarfism. The S249C mutation, found in 33 of the 48 mutated tumors, was the most common. The frequency of mutations was higher in pTa tumors (37 of 50, 74%) than in CIS (0 of 20, 0%; P< 0.0001), pT1 (4 of 19, 21%; P< 0.0001) and pT2–4 tumors (7 of 43, 16%; P< 0.0001). FGFR3mutations were detected in 27 of 32 (84%) G1, 16 of 29 (55%) G2, and 5 of 71 (7%) G3 tumors. This association between FGFR3mutations and low grade was highly significant (P< 0.0001). FGFR3is the first gene found to be mutated at a high frequency in pTa tumors. The absence of FGFR3mutations in CIS and the low frequency of FGFR3mutations in pT1 and pT2–4 tumors are consistent with the model of bladder tumor progression in which the most common precursor of pT1 and pT2–4 tumors is CIS.

Published
2001
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5. EXTERNAL VALIDATION OF THE UPDATED PARTIN TABLES IN A COHORT OF FRENCH AND ITALIAN MEN

Author

Philippe Arjane, Shahrokh F. Shariat, Laurent Salomon, Laurent Zini, Umberto Capitanio, Claude C. Abbou, Nazareno Suardi, Alexandre de la Taille, Naeem Bhojani, Francesco Montorsi, François Péloquin, Claudio Jeldres, Daniel Pharand, Pierre I. Karakiewicz, Bhojani, Naeem, Salomon, Laurent, Capitanio, Umberto, Suardi, Nazareno, Shariat Shahrokh, F., Jeldres, Claudio, Zini, Laurent, Pharand, Daniel, Peloquin, Francoi, Arjane, Philippe, Abbou Claude, C., De La Taille, Alexandre, Montorsi, Francesco, and Karakiewicz Pierre, I.

Subjects
Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Sensitivity and Specificity, Pelvis, Cohort Studies, medicine, Humans, Neoplasm Invasiveness, Radiology, Nuclear Medicine and imaging, Stage (cooking), Neoplasm Staging, Prostatectomy, Gynecology, Radiation, Receiver operating characteristic, business.industry, External validation, Prostatic Neoplasms, Seminal Vesicles, Prostate-Specific Antigen, Prostate-specific antigen, Italy, ROC Curve, Oncology, Partin Tables, Calibration, Cohort, France, Lymph Nodes, business, Demography, Cohort study
Abstract

Purpose: To test the discrimination and calibration properties of the newly developed 2007 Partin Tables in two European cohorts with localized prostate cancer. Methods: Data on clinical and pathologic characteristics were obtained for 1,064 men treated with radical prostatectomy at the Creteil University Health Center in France (n = 839) and at the Milan University Vita-Salute in Italy (n = 225). Overall discrimination was assessed with receiver operating characteristic curve analysis, which quantified the accuracy of stage predictions for each center. Calibration plots graphically explored the relationship between predicted and observed rates of extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion (LNI). Results: The rates of ECE, SVI, and LNI were 28%, 14%, and 2% in the Creteil cohort vs. 11%, 5%, and 5% in the Milan cohort. In the Creteil cohort, the accuracy of ECE, SVI, and LNI prediction was 61%, 71%, and 82% vs. 66%, 92% and 75% for the Milan cohort. Important departures were recorded between Partin Tables' predicted and observed rates of ECE, SVI, and LNI within both cohorts. Conclusions: The 2007 Partin Tables demonstrated worse performance in European men than they originally did in North American men. This indicates that predictive models need to be externally validated before their implementation into clinical practice. (c) 2009 Elsevier Inc.

Published
2009

6. FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder.

Author

Bakkar AA, Wallerand H, Radvanyi F, Lahaye JB, Pissard S, Lecerf L, Kouyoumdjian JC, Abbou CC, Pairon JC, Jaurand MC, Thiery JP, Chopin DK, and de Medina SG

Subjects
Adult, Aged, Aged, 80 and over, Carcinoma, Transitional Cell pathology, Humans, Middle Aged, Neoplasm Staging, Receptor, Fibroblast Growth Factor, Type 3, Urinary Bladder Neoplasms pathology, Carcinoma, Transitional Cell genetics, Genes, p53 genetics, Mutation, Protein-Tyrosine Kinases, Receptors, Fibroblast Growth Factor genetics, Urinary Bladder Neoplasms genetics
Abstract

FGFR3 and TP53 mutations are frequent in superficial papillary and invasive disease, respectively. We used denaturing high-performance liquid chromatography and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed urothelial cell carcinomas. Tumors were classified as follows: 31 pTa, 1 carcinoma in situ, 30 pT1, and 19 pT2-T4. Tumor grades were as follows: 10 G1, 29 G2, and 42 G3. FGFR3 mutations were associated with low-stage (P < 0.0001), low-grade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations define separate pathways at initial diagnosis of urothelial cell carcinoma.

Published
2003

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