title: Prognostic role ofKRASmutations in Sardinian patients with colorectal carcinoma.
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.
authors.affiliation: Institute of Biomolecular Chemistry, CNR, 07100 Sassari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Paliogiannis
authors.affiliation: Oncology Unit, Local Health Unit (ASL1), 07100 Sassari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazzola
authors.affiliation: Oncology Unit, Civil Hospital, 07041 Alghero, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Baldino
authors.affiliation: Department of Medical Oncology, University of Cagliari, 09042 Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.affiliation: Department of Medical Oncology, University of Cagliari, 09042 Cagliari, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ionta
authors.affiliation: Oncology Unit, Local Health Unit (ASL2), 07026 Olbia, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ortu
authors.affiliation: Oncology Unit, Zonchello Hospital, 08100 Nuoro, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Capelli
authors.affiliation: Oncology Unit, Businco Hospital, 09121 Cagliari, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Lanzillo
authors.affiliation: Oncology Unit, Local Health Unit (ASL), 09170 Oristano, Italy.
authors.forename: Tito
authors.initials: T
authors.lastname: Sedda
authors.affiliation: Department of Medical Oncology, Hospital University (AOU), 07100 Sassari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sanna
authors.affiliation: Oncology Unit, Local Health Unit (ASL4), 08045 Lanusei, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Barca
authors.affiliation: Oncology Unit, Local Health Unit (ASL7), 09013 Carbonia-Iglesias, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Virdis
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.affiliation: Institute of Biomolecular Chemistry, CNR, 07100 Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
keywords: KRAS; cancer; colorectal; metastasis; mutations; survival; target therapies