title: Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer.
abstract: BACKGROUND
  In metastatic colorectal cancer (mCRC), BRAFV600E mutation has been variously associated to specific clinico-pathological features.
  
  
  METHODS
  Two large retrospective series of mCRC patients from two Italian Institutions were used as training-set (TS) and validation-set (VS) for developing a nomogram predictive of BRAFV600E status. The model was internally and externally validated.
  
  
  RESULTS
  In the TS, data from 596 mCRC patients were gathered (RAS wild-type (wt) 281 (47.1%); BRAFV600E mutated 54 (9.1%)); RAS and BRAFV600E mutations were mutually exclusive. In the RAS-wt population, right-sided primary (odds ratio (OR): 7.80, 95% confidence interval (CI) 3.05-19.92), female gender (OR: 2.90, 95% CI 1.14-7.37) and mucinous histology (OR: 4.95, 95% CI 1.90-12.90) were independent predictors of BRAFV600E mutation, with high replication at internal validation (100%, 93% and 98%, respectively). A predictive nomogram was calculated: patients with the highest score (right-sided primary, female and mucinous) had a 81% chance to bear a BRAFV600E-mutant tumour; accuracy measures: AUC=0.812, SE:0.034, sensitivity:81.2%; specificity:72.1%. In the VS (508 pts, RAS wt: 262 (51.6%), BRAFV600E mutated: 49 (9.6%)), right-sided primary, female gender and mucinous histology were confirmed as independent predictors of BRAFV600E mutation with high accuracy.
  
  
  CONCLUSIONS
  Three simple and easy-to-collect characteristics define a useful nomogram for predicting BRAF status in mCRC with high specificity and sensitivity.
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Moretto
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria 'Santa Maria della Misericordia', Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Muntoni
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria 'Santa Maria della Misericordia', Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Iacono
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria 'Santa Maria della Misericordia', Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Casagrande
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria 'Santa Maria della Misericordia', Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Salvatore
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Schirripa
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Rossini
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria 'Santa Maria della Misericordia', Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Maglio
authors.affiliation: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria 'Santa Maria della Misericordia', Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: Dipartimento di Medicina, Oncologia Medica, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126 Verona, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Calvetti
authors.affiliation: Dipartimento di Medicina, Oncologia Medica, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126 Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pilotto
authors.affiliation: Dipartimento di Medicina, Oncologia Medica, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126 Verona, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Carbognin
authors.affiliation: Divisione di Patologia, Dipartimento di Chirurgia, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
authors.affiliation: Dipartimento di Medicina, Oncologia Medica, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126 Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Oncologia Medica 2 Universitaria, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.affiliation: Direzione Scientifica, Biostatistics, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Dipartimento di Medicina, Oncologia Medica, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126 Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D049451:Nomograms; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf