Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer

Fotios Loupakis, R. Moretto, Giuseppe Aprile, Marta Muntoni, C. Cremolini, Donatella Iacono, Mariaelena Casagrande, Laura Ferrari, L. Salvatore, M. Schirripa, Daniele Rossini, Giovanna De maglio, Gianpiero Fasola, Lorenzo Calvetti, Sara Pilotto, Luisa Carbognin, Gabriella Fontanini, Giampaolo Tortora, Alfredo Falcone, Isabella SperdutiEmilio Bria

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)30-36
Number of pages7
JournalBritish Journal of Cancer
Issue number1
Publication statusPublished - Jan 12 2016


  • BRAF
  • metastatic colorectal cancer
  • nomogram

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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