Jeanne Netter1, Jacqueline Lehmann-Che2, Jerome Lambert3, Anne Tallet4, Nelson Lourenco1, Hany Soliman2, Philippe Bertheau5, Benjamin Pariente6, Mircea Chirica7, Marc Pocard8, Matthieu Allez6, Hugues De The2, Jean-Marc Gornet9. 1. AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France. 2. AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France; Inserm/CNRS UMR 944/7212, 75010 Paris, France. 3. AP-HP, Saint-Louis Hospital, Department of Biostatistics, 75010 Paris, France; Inserm UMR 717, 75010 Paris, France. 4. AP-HP, Saint-Louis Hospital, Department of Biochemistry, 75010 Paris, France. 5. AP-HP, Saint-Louis Hospital, Department of Pathology, 75010 Paris, France; University Paris Diderot, UMR-S-728 Inserm, 75013 Paris, France. 6. AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France; Équipe Avenir Inserm U940, 75010 Paris, France. 7. AP-HP, Saint-Louis Hospital, Department of General, Endocrine and Digestive Surgery, 75010 Paris, France. 8. Surgical Oncologic and Digestive Unit, Lariboisière Hospital, AP-HP, 75010 Paris, France. 9. AP-HP, Saint-Louis Hospital, Department of Gastroenterology, 75010 Paris, France. Electronic address: jean-marc.gornet@sls.aphp.fr.
Abstract
BACKGROUND: Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting. METHODS: The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients. RESULTS: PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53-mutated and wild type groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53-1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS. CONCLUSIONS: Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC.
BACKGROUND: Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting. METHODS: The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients. RESULTS: PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53-mutated and wild type groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53-1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS. CONCLUSIONS: Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC.
Authors: Jose J G Marin; Rocio I R Macias; Maria J Monte; Elisa Herraez; Ana Peleteiro-Vigil; Beatriz Sanchez de Blas; Paula Sanchon-Sanchez; Alvaro G Temprano; Ricardo A Espinosa-Escudero; Elisa Lozano; Oscar Briz; Marta R Romero Journal: Cancers (Basel) Date: 2020-09-11 Impact factor: 6.639