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1. PD-1 blockade induces responses by inhibiting adaptive immune resistance

Author

Tumeh, Paul C, Harview, Christina L, Yearley, Jennifer H, Shintaku, I Peter, Taylor, Emma JM, Robert, Lidia, Chmielowski, Bartosz, Spasic, Marko, Henry, Gina, Ciobanu, Voicu, West, Alisha N, Carmona, Manuel, Kivork, Christine, Seja, Elizabeth, Cherry, Grace, Gutierrez, Antonio J, Grogan, Tristan R, Mateus, Christine, Tomasic, Gorana, Glaspy, John A, Emerson, Ryan O, Robins, Harlan, Pierce, Robert H, Elashoff, David A, Robert, Caroline, and Ribas, Antoni

Subjects
Aging, Parkinson's Disease, Neurosciences, Brain Disorders, Cancer, Neurodegenerative, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Adaptive Immunity, Aged, Aged, 80 and over, Biomarkers, CD8-Positive T-Lymphocytes, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Humans, Immunotherapy, Male, Melanoma, Middle Aged, Models, Biological, Multivariate Analysis, Programmed Cell Death 1 Receptor, Treatment Outcome, General Science & Technology
Abstract

Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.

Published
2014

3. Supplementary figure 2 from Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

Author

Boussemart, Lise, primary, Girault, Isabelle, primary, Malka-Mahieu, Hélène, primary, Mateus, Christine, primary, Routier, Emilie, primary, Rubington, Margot, primary, Kamsu-Kom, Nyam, primary, Thomas, Marina, primary, Tomasic, Gorana, primary, Agoussi, Sandrine, primary, Breckler, Marie, primary, Laporte, Mélanie, primary, Lacroix, Ludovic, primary, Eggermont, Alexander M., primary, Cavalcanti, Andrea, primary, Grange, Florent, primary, Adam, Julien, primary, Vagner, Stéphan, primary, and Robert, Caroline, primary

Published
2023
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4. Supplementary Figure Legends 1-2 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Author

Arnault, Jean Philippe, primary, Mateus, Christine, primary, Escudier, Bernard, primary, Tomasic, Gorana, primary, Wechsler, Janine, primary, Hollville, Emilie, primary, Soria, Jean-Charles, primary, Malka, David, primary, Sarasin, Alain, primary, Larcher, Magalie, primary, André, Jocelyne, primary, Kamsu-Kom, Nyam, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Spatz, Alain, primary, Eggermont, Alexander M., primary, Druillennec, Sabine, primary, Vagner, Stephan, primary, Eychène, Alain, primary, Dumaz, Nicolas, primary, and Robert, Caroline, primary

Published
2023
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5. Supplementary Information from A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents

Author

Azan, Antoine, primary, Caspers, Peter J., primary, Bakker Schut, Tom C., primary, Roy, Séverine, primary, Boutros, Céline, primary, Mateus, Christine, primary, Routier, Emilie, primary, Besse, Benjamin, primary, Planchard, David, primary, Seck, Atmane, primary, Kamsu Kom, Nyam, primary, Tomasic, Gorana, primary, Koljenović, Senada, primary, Noordhoek Hegt, Vincent, primary, Texier, Matthieu, primary, Lanoy, Emilie, primary, Eggermont, Alexander M.M., primary, Paci, Angelo, primary, Robert, Caroline, primary, Puppels, Gerwin J., primary, and Mir, Lluis M., primary

Published
2023
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6. Supplementary Table S2 from A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents

Author

Azan, Antoine, primary, Caspers, Peter J., primary, Bakker Schut, Tom C., primary, Roy, Séverine, primary, Boutros, Céline, primary, Mateus, Christine, primary, Routier, Emilie, primary, Besse, Benjamin, primary, Planchard, David, primary, Seck, Atmane, primary, Kamsu Kom, Nyam, primary, Tomasic, Gorana, primary, Koljenović, Senada, primary, Noordhoek Hegt, Vincent, primary, Texier, Matthieu, primary, Lanoy, Emilie, primary, Eggermont, Alexander M.M., primary, Paci, Angelo, primary, Robert, Caroline, primary, Puppels, Gerwin J., primary, and Mir, Lluis M., primary

Published
2023
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7. Table S1 from Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

Author

Boussemart, Lise, primary, Girault, Isabelle, primary, Malka-Mahieu, Hélène, primary, Mateus, Christine, primary, Routier, Emilie, primary, Rubington, Margot, primary, Kamsu-Kom, Nyam, primary, Thomas, Marina, primary, Tomasic, Gorana, primary, Agoussi, Sandrine, primary, Breckler, Marie, primary, Laporte, Mélanie, primary, Lacroix, Ludovic, primary, Eggermont, Alexander M., primary, Cavalcanti, Andrea, primary, Grange, Florent, primary, Adam, Julien, primary, Vagner, Stéphan, primary, and Robert, Caroline, primary

Published
2023
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8. Supplementary Figure 1 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Author

Arnault, Jean Philippe, primary, Mateus, Christine, primary, Escudier, Bernard, primary, Tomasic, Gorana, primary, Wechsler, Janine, primary, Hollville, Emilie, primary, Soria, Jean-Charles, primary, Malka, David, primary, Sarasin, Alain, primary, Larcher, Magalie, primary, André, Jocelyne, primary, Kamsu-Kom, Nyam, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Spatz, Alain, primary, Eggermont, Alexander M., primary, Druillennec, Sabine, primary, Vagner, Stephan, primary, Eychène, Alain, primary, Dumaz, Nicolas, primary, and Robert, Caroline, primary

Published
2023
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9. Supplementary Figures legends from Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

Author

Boussemart, Lise, primary, Girault, Isabelle, primary, Malka-Mahieu, Hélène, primary, Mateus, Christine, primary, Routier, Emilie, primary, Rubington, Margot, primary, Kamsu-Kom, Nyam, primary, Thomas, Marina, primary, Tomasic, Gorana, primary, Agoussi, Sandrine, primary, Breckler, Marie, primary, Laporte, Mélanie, primary, Lacroix, Ludovic, primary, Eggermont, Alexander M., primary, Cavalcanti, Andrea, primary, Grange, Florent, primary, Adam, Julien, primary, Vagner, Stéphan, primary, and Robert, Caroline, primary

Published
2023
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10. Supplementary Figure 2 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Author

Arnault, Jean Philippe, primary, Mateus, Christine, primary, Escudier, Bernard, primary, Tomasic, Gorana, primary, Wechsler, Janine, primary, Hollville, Emilie, primary, Soria, Jean-Charles, primary, Malka, David, primary, Sarasin, Alain, primary, Larcher, Magalie, primary, André, Jocelyne, primary, Kamsu-Kom, Nyam, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Spatz, Alain, primary, Eggermont, Alexander M., primary, Druillennec, Sabine, primary, Vagner, Stephan, primary, Eychène, Alain, primary, Dumaz, Nicolas, primary, and Robert, Caroline, primary

Published
2023
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11. Data from A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents

Author

Azan, Antoine, primary, Caspers, Peter J., primary, Bakker Schut, Tom C., primary, Roy, Séverine, primary, Boutros, Céline, primary, Mateus, Christine, primary, Routier, Emilie, primary, Besse, Benjamin, primary, Planchard, David, primary, Seck, Atmane, primary, Kamsu Kom, Nyam, primary, Tomasic, Gorana, primary, Koljenović, Senada, primary, Noordhoek Hegt, Vincent, primary, Texier, Matthieu, primary, Lanoy, Emilie, primary, Eggermont, Alexander M.M., primary, Paci, Angelo, primary, Robert, Caroline, primary, Puppels, Gerwin J., primary, and Mir, Lluis M., primary

Published
2023
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12. Supplementary figure 1 from Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

Author

Boussemart, Lise, primary, Girault, Isabelle, primary, Malka-Mahieu, Hélène, primary, Mateus, Christine, primary, Routier, Emilie, primary, Rubington, Margot, primary, Kamsu-Kom, Nyam, primary, Thomas, Marina, primary, Tomasic, Gorana, primary, Agoussi, Sandrine, primary, Breckler, Marie, primary, Laporte, Mélanie, primary, Lacroix, Ludovic, primary, Eggermont, Alexander M., primary, Cavalcanti, Andrea, primary, Grange, Florent, primary, Adam, Julien, primary, Vagner, Stéphan, primary, and Robert, Caroline, primary

Published
2023
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13. Supplementary Figure S1 from A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents

Author

Azan, Antoine, primary, Caspers, Peter J., primary, Bakker Schut, Tom C., primary, Roy, Séverine, primary, Boutros, Céline, primary, Mateus, Christine, primary, Routier, Emilie, primary, Besse, Benjamin, primary, Planchard, David, primary, Seck, Atmane, primary, Kamsu Kom, Nyam, primary, Tomasic, Gorana, primary, Koljenović, Senada, primary, Noordhoek Hegt, Vincent, primary, Texier, Matthieu, primary, Lanoy, Emilie, primary, Eggermont, Alexander M.M., primary, Paci, Angelo, primary, Robert, Caroline, primary, Puppels, Gerwin J., primary, and Mir, Lluis M., primary

Published
2023
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14. Supplementary Figures 1 - 5 from Vemurafenib Cooperates with HPV to Promote Initiation of Cutaneous Tumors

Author

Holderfield, Matthew, primary, Lorenzana, Edward, primary, Weisburd, Ben, primary, Lomovasky, Lisa, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Tomasic, Gorana, primary, Favre, Michel, primary, Vagner, Stephan, primary, Robert, Caroline, primary, Ghoddusi, Majid, primary, Daniel, Dylan, primary, Pryer, Nancy, primary, McCormick, Frank, primary, and Stuart, Darrin, primary

Published
2023
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15. Data from Vemurafenib Cooperates with HPV to Promote Initiation of Cutaneous Tumors

Author

Holderfield, Matthew, primary, Lorenzana, Edward, primary, Weisburd, Ben, primary, Lomovasky, Lisa, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Tomasic, Gorana, primary, Favre, Michel, primary, Vagner, Stephan, primary, Robert, Caroline, primary, Ghoddusi, Majid, primary, Daniel, Dylan, primary, Pryer, Nancy, primary, McCormick, Frank, primary, and Stuart, Darrin, primary

Published
2023
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16. Supplementary Table 1 from Vemurafenib Cooperates with HPV to Promote Initiation of Cutaneous Tumors

Author

Holderfield, Matthew, primary, Lorenzana, Edward, primary, Weisburd, Ben, primary, Lomovasky, Lisa, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Tomasic, Gorana, primary, Favre, Michel, primary, Vagner, Stephan, primary, Robert, Caroline, primary, Ghoddusi, Majid, primary, Daniel, Dylan, primary, Pryer, Nancy, primary, McCormick, Frank, primary, and Stuart, Darrin, primary

Published
2023
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17. eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies

Author

Boussemart, Lise, Malka-Mahieu, Helene, Girault, Isabelle, Allard, Delphine, Hemmingsson, Oskar, Tomasic, Gorana, Thomas, Marina, Basmadjian, Christine, Ribeiro, Nigel, Thuaud, Frederic, Mateus, Christina, Routier, Emilie, Kamsu-Kom, Nyam, Agoussi, Sandrine, Eggermont, Alexander M., Desaubry, Laurent, Robert, Caroline, and Vagner, Stephan

Subjects
Antineoplastic agents -- Health aspects -- Research, Vemurafenib -- Research, Drug resistance -- Research, Protein research, Pharmaceutical research, Antimitotic agents -- Health aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3)K-AKT-mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade (1-3). All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the 7-methylguanylate cap (m7G) at the 5' end of messenger RNA, thereby modulating the translation of specific mRNAs (4,5). Here we show that the persistent formation of the eIF4F complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and anti-BRAF plus anti-MEK drug combinations in BRAF(V600)-mutant melanoma, colon and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with one of three mechanisms: reactivation of MAPK signalling, persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 or increased pro-apoptotic BCL-2-modifying factor (BMF)-dependent degradation of eIF4G. The development of an insitumethod to detect the eIF4E-eIF4G interactions shows that eIF4F complex formation is decreased in tumours that respond to anti-BRAF therapy and increased in resistant metastases compared to tumours before treatment. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A, synergizes with inhibiting BRAF(V600) to kill the cancer cells. eIF4F not only appears to be an indicator of both innate and acquired resistance but also is a promising therapeutic target. Combinations of drugs targeting BRAF (and/or MEK) andeIF4F may overcome most of the resistance mechanisms arising in BRAF(V600)-mutant cancers., A plethora of mechanisms of resistance to BRAF(V600) inhibitors have been described, including mutations of NRAS, MAP2K1 and PIK3CA, partial deletion of PTEN, expression of BRAF splice variants, upregulation of [...]

Published
2014

20. Quiz

Author

Athanasiou, Alexandra, Vanel, Daniel, Tomasic, Gorana, Bidault, Francois, and Balleyguier, Corinne

Published
2007
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37. Cervical cytopathology: an evaluation of its accuracy based on cytohistologic comparison

Author

DiBonito, Luigi, Falconieri, Giovanni, Tomasic, Gorana, Colautti, Isabella, Bonifacio, Daniela, and Dudine, Sandra

Subjects
Pap test -- Evaluation, Cervical cancer -- Diagnosis, Cancer -- Cytopathology, Cytodiagnosis -- Evaluation, Cervix dysplasia -- Diagnosis, Health
Abstract

Background. Although Papanicolaou cytology represents the most effective technique to prevent and detect precancerous conditions of the uterine cervix, its false-negative yield is still a reason of concern among pathologists and gynecologists. Methods. Because histologic control is one of the best ways to assess the accuracy of cytology diagnosis, the authors have investigated 1000 women who had cervical smears and tissue sampling obtained during the same colposcopic evaluation between 1987 and 1990. Results. Out of 1000 cases (average age, 34.6 years; range, 14-80 years), 918 had adequate, 62 had less than optimal, and 10 had unsatisfactory samples. Cytology unsatisfactory and less than optimal cases as well as inadequate histology cases have been disregarded from all calculations. After histologic comparison, confirmed negatives were 622 of 918 (67.8%). Cytologic diagnoses of cervical intra-epithelial neoplasia (CIN) I were 96, of CIN II were 44, of CIN III, inclusive of carcinoma in situ, were 39, and of invasive carcinoma were 2. Atypical cases were 56. The overall sensitivity was 76.3%, with group sensitivity rates increasing directly with CIN grade. Positive predictive value was 80.2%. Specificity was 93.0%, and negative predictive value was 91.3%. False-negatives were 59 of 681 (8.7%), basically due to sampling errors. Among true-positives, there was 1 category discrepancy in 30 cases (mostly undercalled or overcalled CIN II) and 2 category discrepancies in 4 cases. Conclusions. Cervical cytology has an overall accuracy close to that reported in studies employing indirect control methods, such as patient follow-up. Higher sensitivity rates emerged for CIN II, CIN III, and cervical carcinoma. Our figures of sensitivity and specificity may represent a useful reference source for future studies dealing with quality control in cervical cytopathology.

Published
1993

38. A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents

Author

Azan, Antoine, primary, Caspers, Peter J., additional, Bakker Schut, Tom C., additional, Roy, Séverine, additional, Boutros, Céline, additional, Mateus, Christine, additional, Routier, Emilie, additional, Besse, Benjamin, additional, Planchard, David, additional, Seck, Atmane, additional, Kamsu Kom, Nyam, additional, Tomasic, Gorana, additional, Koljenović, Senada, additional, Noordhoek Hegt, Vincent, additional, Texier, Matthieu, additional, Lanoy, Emilie, additional, Eggermont, Alexander M.M., additional, Paci, Angelo, additional, Robert, Caroline, additional, Puppels, Gerwin J., additional, and Mir, Lluis M., additional

Published
2016
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39. Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

Author

Boussemart, Lise, primary, Girault, Isabelle, additional, Malka-Mahieu, Hélène, additional, Mateus, Christine, additional, Routier, Emilie, additional, Rubington, Margot, additional, Kamsu-Kom, Nyam, additional, Thomas, Marina, additional, Tomasic, Gorana, additional, Agoussi, Sandrine, additional, Breckler, Marie, additional, Laporte, Mélanie, additional, Lacroix, Ludovic, additional, Eggermont, Alexander M., additional, Cavalcanti, Andrea, additional, Grange, Florent, additional, Adam, Julien, additional, Vagner, Stéphan, additional, and Robert, Caroline, additional

Published
2016
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40. Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma

Author

Tejera-Vaquerizo, Antonio, primary, Nagore, Eduardo, additional, Puig, Susana, additional, Robert, Caroline, additional, Saiag, Philippe, additional, Martín-Cuevas, Paula, additional, Gallego, Elena, additional, Herrera-Acosta, Enrique, additional, Aguilera, José, additional, Malvehy, Josep, additional, Carrera, Cristina, additional, Cavalcanti, Andrea, additional, Rull, Ramón, additional, Vilalta-Solsona, Antonio, additional, Lannoy, Emilie, additional, Boutros, Celine, additional, Benannoune, Naima, additional, Tomasic, Gorana, additional, Aegerte, Philippe, additional, Vidal-Sicart, Sergi, additional, Palou, Josep, additional, Alos, LLúcia, additional, Requena, Celia, additional, Traves, Víctor, additional, Pla, Ángel, additional, Bolumar, Isidro, additional, Soriano, Virtudes, additional, Guillén, Carlos, additional, and Herrera-Ceballos, Enrique, additional

Published
2015
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42. Abstract 934: BRAF inhibitors induce skin and extra-cutaneous tumors via paradoxical activation of the MAPK pathway: Molecular study of 66 tumors and visualization of BRAF/CRAF protein dimers

Author

Boussemart, Lise, primary, Girault, Isabelle, additional, Mateus, Christine, additional, Thomas, Marina, additional, Routier, Emilie, additional, Cazenave, Hugo, additional, Tomasic, Gorana, additional, Wechlser, Janine, additional, Kamsu-Kom, Nyam, additional, Roy, Séverine, additional, Favre, Michel, additional, Lacroix, Ludovic, additional, Eggermont, Alexander, additional, Vagner, Stéphan, additional, and Robert, Caroline, additional

Published
2014
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43. Melanoma Arising From a Long-Standing Pigmented Trichoblastoma

Author

Benaïm, Gilles, primary, Castillo, Christine, additional, Houang, Michelle, additional, Dejardin, Lydia, additional, Mateus, Christine, additional, Wang, Qing, additional, Pissaloux, Daniel, additional, Tomasic, Gorana, additional, Cribier, Bernard, additional, and de la Fouchardière, Arnaud, additional

Published
2014
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44. Vemurafenib Cooperates with HPV to Promote Initiation of Cutaneous Tumors

Author

Holderfield, Matthew, primary, Lorenzana, Edward, additional, Weisburd, Ben, additional, Lomovasky, Lisa, additional, Boussemart, Lise, additional, Lacroix, Ludovic, additional, Tomasic, Gorana, additional, Favre, Michel, additional, Vagner, Stephan, additional, Robert, Caroline, additional, Ghoddusi, Majid, additional, Daniel, Dylan, additional, Pryer, Nancy, additional, McCormick, Frank, additional, and Stuart, Darrin, additional

Published
2014
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45. Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer

Author

Andre, Fabrice, Conforti, Rosa, Arnedos, Monica, Berrada, Narjiss, Delaloge, Suzette, Spielmann, Marc, Moeder, Christopher C.B., Rimm, David D.L., Mauguen, Audrey, Michiels, Stefan, Tomasic, Gorana, Esteva, Francisco F.J., Andre, Fabrice, Conforti, Rosa, Arnedos, Monica, Berrada, Narjiss, Delaloge, Suzette, Spielmann, Marc, Moeder, Christopher C.B., Rimm, David D.L., Mauguen, Audrey, Michiels, Stefan, Tomasic, Gorana, and Esteva, Francisco F.J.

Abstract

Background: The purpose of this study was to evaluate the prognostic and predictive value of p27 expression in patients with early breast cancer. Patients and methods: Quantitative immunofluorescence assays for p27 were done on a tissue microarray that included 823 samples from patients randomized between anthracycline-based chemotherapy and no chemotherapy. Quantification of p27 was done using the AQUA® system (HistoRx, Inc. Branford, CT). Both p27 nuclear expression and the nuclear to cytoplasmic ratio were assessed. Results: Nuclear p27 expression was not predictive for the efficacy of anthracycline-based chemotherapy [adjusted P = 0.18 for disease-free survival (DFS)] nor prognostic [95% confidence interval (CI) 0.99-1.01, P = 0.49]. However, p27 nuclear/cytoplasmic ratio was predictive for the efficacy of adjuvant chemotherapy (adjusted P = 0.016 DFS). The adjusted hazard ratio (HR) for relapse associated with adjuvant chemotherapy was 0.56 (95% CI 0.37-0.84, P = 0.005) and 1.06 (95% CI 0.76-1.47, P = 0.74) for patients with high and low nuclear/cytoplasmic ratio, respectively. p27 N/C ratio was prognostic in patients treated with chemotherapy (HR for relapse or death for a 1 unit increase in p27 N/C ratio was 0.30, 95% CI 0.12-0.77) but not in the untreated arm (HR for relapse or death was 1.27, 95% CI 0.58-2.8). Conclusions: This study did not confirm the role of p27 nuclear expression as a prognostic parameter. However, the p27 nuclear/cytoplasmic ratio was predictive in patients treated with anthracycline-based chemotherapy. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2012

46. Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Author

Arnault, Jean Philippe, primary, Mateus, Christine, additional, Escudier, Bernard, additional, Tomasic, Gorana, additional, Wechsler, Janine, additional, Hollville, Emilie, additional, Soria, Jean-Charles, additional, Malka, David, additional, Sarasin, Alain, additional, Larcher, Magalie, additional, André, Jocelyne, additional, Kamsu-Kom, Nyam, additional, Boussemart, Lise, additional, Lacroix, Ludovic, additional, Spatz, Alain, additional, Eggermont, Alexander M., additional, Druillennec, Sabine, additional, Vagner, Stephan, additional, Eychène, Alain, additional, Dumaz, Nicolas, additional, and Robert, Caroline, additional

Published
2012
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49. CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence

Author

Andre, Fabrice, primary, Xia, Weiya, additional, Conforti, Rosa, additional, Wei, Yongkun, additional, Boulet, Thomas, additional, Tomasic, Gorana, additional, Spielmann, Marc, additional, Zoubir, Moustafa, additional, Berrada, Narjiss, additional, Arriagada, Rodrigo, additional, Hortobagyi, Gabriel N., additional, Hung, Mien-Chie, additional, Pusztai, Lajos, additional, Delaloge, Suzette, additional, Michiels, Stefan, additional, and Cristofanilli, Massimo, additional

Published
2009
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50. Keratoacanthomas and Squamous Cell Carcinomas in Patients Receiving Sorafenib

Author

Arnault, Jean Philippe, primary, Wechsler, Janine, additional, Escudier, Bernard, additional, Spatz, Alain, additional, Tomasic, Gorana, additional, Sibaud, Vincent, additional, Aractingi, Selim, additional, Grange, Jean-Didier, additional, Poirier-Colame, Vichnou, additional, Malka, David, additional, Soria, Jean-Charles, additional, Mateus, Christine, additional, and Robert, Caroline, additional

Published
2009
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