CK7 and consensus molecular subtypes as major prognosticators in V600E BRAF mutated metastatic colorectal cancer

Fotios Loupakis, Paola Biason, Alessandra Anna Prete, Chiara Cremolini, Filippo Pietrantonio, Nicoletta Pella, Emanuela Dell’Aquila, Elisa Sperti, Clizia Zichi, Rossana Intini, Vincenzo Dadduzio, Marta Schirripa, Francesca Bergamo, Carlotta Antoniotti, Federica Morano, Francesco Cortiula, Giovanna De Maglio, Lorenza Rimassa, Valeria Smiroldo, Lorenzo CalvettiGiuseppe Aprile, Lisa Salvatore, Daniele Santini, Giada Munari, Roberta Salmaso, Vincenza Guzzardo, Claudia Mescoli, Sara Lonardi, Massimo Rugge, Vittorina Zagonel, Massimo Di Maio, Matteo Fassan

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Abstract

Background: V600EBRAF mutated metastatic colorectal cancer (mCRC) is a subtype (10%) with overall poor prognosis, but the clinical experience suggests a great heterogeneity in survival. It is still unexplored the real distribution of traditional and innovative biomarkers among V600EBRAF mutated mCRC and which is their role in the improvement of clinical prediction of survival outcomes. Methods: Data and tissue specimens from 155 V600EBRAF mutated mCRC patients treated at eight Italian Units of Oncology were collected. Specimens were analysed by means of immunohistochemistry profiling performed on tissue microarrays. Primary endpoint was overall survival (OS). Results: CDX2 loss conferred worse OS (HR = 1.72, 95%CI 1.03–2.86, p = 0.036), as well as high CK7 expression (HR = 2.17, 95%CI 1.10–4.29, p = 0.026). According to Consensus Molecular Subtypes (CMS), CMS1 patients had better OS compared to CMS2-3/CMS4 (HR = 0.37, 95%CI 0.19–0.71, p = 0.003). Samples showing less TILs had worse OS (HR = 1.72, 95%CI 1.16–2.56, p = 0.007). Progression-free survival analyses led to similar results. At multivariate analysis, CK7 and CMS subgrouping retained their significant correlation with OS. Conclusion: The present study provides new evidence on how several well-established biomarkers perform in a homogenousV600EBRAF mutated mCRC population, with important and independent information added to standard clinical prognosticators. These data could be useful to inform further translational research, for patients’ stratification in clinical trials and in routine clinical practice to better estimate patients’ prognosis.
Original languageEnglish
Pages (from-to)593-599
Number of pages7
JournalBritish Journal of Cancer
Volume121
Issue number7
DOIs
Publication statusPublished - Oct 1 2019

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Loupakis, F., Biason, P., Prete, A. A., Cremolini, C., Pietrantonio, F., Pella, N., Dell’Aquila, E., Sperti, E., Zichi, C., Intini, R., Dadduzio, V., Schirripa, M., Bergamo, F., Antoniotti, C., Morano, F., Cortiula, F., De Maglio, G., Rimassa, L., Smiroldo, V., ... Fassan, M. (2019). CK7 and consensus molecular subtypes as major prognosticators in V600E BRAF mutated metastatic colorectal cancer. British Journal of Cancer, 121(7), 593-599. https://doi.org/10.1038/s41416-019-0560-0