Francesca V Negri1, Pellegrino Crafa2, Giuseppe Pedrazzi3, Cecilia Bozzetti1, Costanza Lagrasta2, Giorgio Gardini4, Ione Tamagnini4, Alessandra Bisagni4, Cinzia Azzoni2, Lorena Bottarelli2, Gallia Graiani2, Ida Romano5, Rosa Porzio6, Gian P Bacchini1, Carlo Paties7, Gianluca Tomasello8, Giovanni Marchetti9, Silvia Fanello10, Carmine Pinto1, Roberto Sala11, Andrea Ardizzoni12. 1. Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy. 2. Department of Pathology, University Hospital, Via Gramsci 14, 43126 Parma, Italy. 3. Department of Neuroscience, University of Parma, Via Volturno 39, 43126 Parma, Italy. 4. Pathology Unit, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, Viale Umberto I 50, 42123 Reggio Emilia, Italy. 5. Department of Radiology, University Hospital, Via Gramsci 14, 43126 Parma, Italy. 6. Medical Oncology Unit, Azienda Unità Sanitaria Locale, Via Taverna 49, 29121 Piacenza, Italy. 7. Pathology Unit, Azienda Unità Sanitaria Locale, Via Taverna 49, 29121 Piacenza, Italy. 8. Medical Oncology Unit, Azienda Istituti Ospitalieri, Viale Concordia 1, 26100 Cremona, Italy. 9. Pathology Unit, Azienda Ospedaliera S.Maria Terni, Viale Tristano di Joannuccio 1, 05100 Terni, Italy. 10. Medical Oncology Unit, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, Viale Umberto I 50, 42123 Reggio Emilia, Italy. 11. Department of Biomedical Biotechnological & Translational Sciences (S.Bi.Bi.T), University of Parma, Via Volturno 39, 43126 Parma, Italy. 12. Medical Oncology Unit, St Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna, Italy.
Abstract
AIM: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). MATERIALS & METHODS: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. RESULTS: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. CONCLUSION: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.
AIM: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). MATERIALS & METHODS: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. RESULTS: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. CONCLUSION: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.
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Keywords:
DLL4; Notch activation; bevacizumab; colorectal cancer