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. 2016 Aug;12(2):1415-1421.
doi: 10.3892/ol.2016.4798. Epub 2016 Jun 29.

Prognostic role of KRAS mutations in Sardinian patients with colorectal carcinoma

Grazia Palomba  1 , Antonio Cossu  2 , Panagiotis Paliogiannis  2 , Antonio Pazzola  3 , Giovanni Baldino  4 , Mario Scartozzi  5 , Maria Teresa Ionta  5 , Salvatore Ortu  6 , Francesca Capelli  7 , Annamaria Lanzillo  8 , Tito Sedda  9 , Giovanni Sanna  10 , Michela Barca  11 , Luciano Virdis  12 , Mario Budroni  2 , Giuseppe Palmieri  1
Affiliations

Prognostic role of KRAS mutations in Sardinian patients with colorectal carcinoma

Grazia Palomba et al. Oncol Lett. 2016 Aug.

Abstract

The presence of mutations in the KRAS gene is a predictor of a poor clinical response to EGFR-targeted agents in patients affected by colorectal cancer (CRC), but its significance as a global prognostic factor remains unclear. The aim of the present study was to evaluate the impact of the KRAS mutational status on time to first metastasis (TTM) and overall survival (OS) in a cohort of Sardinian CRC patients. A total of 551 patients with metastatic CRC at the time of enrolment were included. Clinical and pathological features of the disease, including follow-up information, were obtained from medical records and cancer registry data. For mutational analysis formalin-fixed paraffin-embedded tissue samples were processed using a standard protocol. The coding sequence and splice junctions of exons 2 and 3 of the KRAS gene were screened for mutations by direct automated sequencing. Overall, 186 KRAS mutations were detected in 183/551 (33%) patients: 125 (67%) were located in codon 12, 36 (19%) in codon 13, and 18 (10%) in codon 61. The remaining mutations (7; 4%) were detected in uncommonly-affected codons. No significant correlation between KRAS mutations and gender, age, anatomical location and stage of the disease at the time of diagnosis was identified. Furthermore, no prognostic value of KRAS mutations was found considering either TTM or OS. When patients were stratified by KRAS mutational status and gender, males were significantly associated with a longer TTM. The results of the present study indicate that KRAS mutation correlated with a slower metastatic progression in males with CRC from Sardinia, irrespective of the age at diagnosis and the codon of the mutation.

Keywords: KRAS; cancer; colorectal; metastasis; mutations; survival; target therapies.

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Figures

Figure 1.
Figure 1.
Types and frequencies of the mutations observed in the cohort.
Figure 2.
Figure 2.
Mutations in uncommonly-affected codons of the KRAS gene found in the cohort.
Figure 3.
Figure 3.
(A) Time to first metastasis and (B) overall survival according to gender in patients harboring KRAS mutations.
See this image and copyright information in PMC

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