BRAF Mutation Analysis has Clinical Value in Stage III Colon Carcinoma

September 23, 2009
Christina T. Loguidice

In a poster presented at the ECCO 15 - ESMO 34 Joint Congress, Arantza Fariña, MD, and colleagues from the PAMM Laboratory for Pathology and Catharina Hospital Eindhoven, the Netherlands, noted that stage III colon carcinoma patients with the BRAF V600E mutation had a significantly worse prognosis.

In a poster presented at the ECCO 15 - ESMO 34 Joint Congress, Arantza Fariña, MD, and colleagues from the PAMM Laboratory for Pathology and Catharina Hospital Eindhoven, the Netherlands, noted that stage III colon carcinoma patients with the BRAF V600E mutation had a significantly worse prognosis. These findings were based on the results of a study that aimed to assess the impact of microsatellite instability (MSI) positivity and the presence of KRAS and BRAF mutations on colon carcinoma patients.

MSI is a known genetic aberration of colon carcinoma, and these tumors differ from chromosomal instable tumors. KRAS mutations are fairly common in colon carcinoma and constitute early events in the adenoma carcinoma sequence, whereas BRAF is a downstream effector of KRAS. Tumors with BRAF mutations are more frequently right-sided, poorly differentiated, and MSI-positive.

Fariña and colleagues’ study included 258 patients with stage III colon cancer who were treated with surgery followed by a 5-fluorouracil-based adjuvant therapy. DNA was isolated from selected tumor areas of paraffin material after the percentage of tumor cells was determined (range, 30%-90%). BRAF V600E mutations were assessed using a real-time polymerase chain reaction (PCR) test with specific probes for the mutated and the wild-type allele. KRAS mutations in codons 12 and 13 were determined by PCR followed by direct sequencing, and MSI status was determined by typing the BAT 26 marker, which is positive in 99% of MSI-positive white patients.

A Cox proportional hazards regression analysis revealed that BRAF V600E mutation confers a significant worse prognosis in patients with stage III colon carcinoma (HR, 0.384; CI, 0.192-0.768; P = .007). Based on the findings, the authors conclude that tumor mutational status should be determined to predict survival more accurately in patients with colon carcinoma.

ECCO/ESMO Poster 6114

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