Impact of KRAS, BRAF, PIK3CA, TP53 status and ... - Semantic Scholar

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We determined prognostic impact of KRAS, BRAF, PIK3CA and TP53 mutation status and mutation heterogeneity among 164 colorectal cancer (CRC) patients ...
IJC International Journal of Cancer

Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases Inger Marie Løes1,2, Heike Immervoll3, Halfdan Sorbye1,2, Jon-Helge Angelsen4,5, Arild Horn5, Stian Knappskog1,2 and Per Eystein Lønning1,2 1

Department of Clinical Science, University of Bergen, Bergen, Norway Department of Oncology, Haukeland University Hospital, Bergen, Norway 3 Department of Pathology, A˚lesund Hospital, A˚lesund, Norway 4 Department of Clinical Medicine, University of Bergen, Bergen, Norway 5 Department of Digestive Surgery, Haukeland University Hospital, Bergen, Norway

We determined prognostic impact of KRAS, BRAF, PIK3CA and TP53 mutation status and mutation heterogeneity among 164 colorectal cancer (CRC) patients undergoing liver resections for metastatic disease. Mutation status was determined by Sanger sequencing of a total of 422 metastatic deposits. In univariate analysis, KRAS (33.5%), BRAF (6.1%) and PIK3CA (13.4%) mutations each predicted reduced median time to relapse (TTR) (7 vs. 22, 3 vs. 16 and 4 vs. 17 months; p < 0.001, 0.002 and 0.023, respectively). KRAS and BRAF mutations also predicted a reduced median disease-specific survival (DSS) (29 vs. 51 and 16 vs. 49 months; p 65 years)

1.08

(0.71, 1.65)

0.720

0.72

(0.45, 1.17)

0.183

Sex (male vs. female)

0.93

(0.62, 1.40)

0.726

0.98

(0.62, 1.57)

0.942

Nodal status of primary (N1 vs. N0)

1.55

(0.97, 2.48)

0.064

1.99

(1.13, 3.53)

0.018

Synchronous vs. metachronous mets.

2.00

(1.21, 3.29)

0.007

1.58

(0.90, 2.77)

0.110

Multiple vs. single mets.

1.73

(1.11, 2.68)

0.015

1.55

(0.93, 2.58)

0.095

TP53 mutations

0.92

(0.61,1.42)

0.720

0.78

(0.47,1.28)

0.318

PIK3CA mutations

1.12

(0.63, 1.97)

0.700

0.78

(0.40, 1.51)

0.451

KRAS or BRAF mutations (mut vs. double wt)

2.34

(1.50, 3.66)