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Prognostic significance of alterations in KRAS isoforms KRAS-4A/4B and KRAS mutations in colorectal carcinoma
The Journal of Pathology, 10/16/09

Abubaker J et al. – These results highlight the differential role of KRAS isoforms in CRC, their utility as a prognostic biomarker, and underline the importance of KRAS alterations as a potential therapeutic target for CRC.

Methods

285 CRC cases analysed for KRAS mutation by direct DNA sequencing followed by immunohistochemical analysis after validation with real-time PCR assay to study the protein expression of KRAS4A and -4B isoforms

Results

KRAS gene mutations seen in 80/285 CRCs (28.1%) and of the mutated cases, the majority of the mutations were seen in codon 12 (81.2%) as opposed to codon 13 (18.8%)
CRCs with KRAS mutations associated with poor overall survival
KRAS mutations at codon 12 associated with poor overall survival of 64.4% at 5 years compared with a 5-year overall survival of 75.8% and 78.2% with codon 13 mutation and absence of KRAS mutations
KRAS4A protein expression predominantly seen in cytoplasm, while KRAS4B protein was nuclear
KRAS4A overexpression significantly associated with left colon, histology subtype of adenocarcinoma, p27kip1, and cleaved caspase3 expression.
Both KRAS mutation and KRAS4A independent prognostic markers in multivariate analysis with age, gender, stage, differentiation, and MSI status

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