Author(s): Elena Puerta-García aff1 , Marisa Cañadas-Garre [*] aff1 , Miguel Ángel Calleja-Hernández aff1
BRAF; colorectal carcinoma; KRAS
Colorectal cancer (CRC) is the third leading cause of death for both sexes in the USA [1 ], and the second in Europe [2 ]. The incidence rate has increased since 1975 both in men and women, although there has been a decline in the overall incidence during the past decade (2001-2010) [1 ]. In Europe, a decline in mortality rates of 26% in males and 20% females has been predicted for 2014 [3 ]. CRC showed the highest incidence for both sexes while lung cancer presented the highest death rates [4 ].
Several causes have been proposed to explain the decline in CRC death rates, such as changes in life style leading to decrease in exposure to risk factors, mainly tobacco use; improvement in screening programs, particularly regarding to closer surveillance of patients in risk and higher adherence to screening tests; finally, treatment outcome has improved, mainly due to the incorporation of new therapeutic approaches, such as monoclonal antibody therapies [5 ].
TNM staging system
The TNM (tumor, node, metastases) system is the method of staging neoplasms developed by the AJCC (American Joint Committee on Cancer). Table 1 shows TNM staging system for CRC, according to the 2010 update (7th Edition) [ 6,7 ]. The TNM system is a useful tool to establish the initial prognosis and make therapeutic decisions. It is based on the hypothesis that tumors from the same source and histology present similar growth and expansion patterns [ 8 ]. It should be noted that the criteria used for histopathological staging in CRC have varied over time. The correct determination of nodal metastases when differentiating stage II (node negative) from stage III (node positive) is particularly important to establish prognosis and treatment. The number of nodes needed to be examined was debated for quite some time, but it was not until 1990 when the consensus decision to examine at least 12 lymph nodes to properly classify a tumor as stage II was adopted, and not incorporated until the TNM staging system 4th Edition (1992) [9 ]. Therefore, some studies published before this consensus are susceptible of have incorrectly understaged those cases in which less than 12 lymph nodes had been examined [10,11 ]. In addition, the behavior of CRC tumors does not always reflect the pathophysiological characteristics corresponding to the TNM level [ 12 ]. CRC is a result of an accumulation of both genomic and epigenomic alterations, so the phenotype is the product of the information contained in the genome, regulated and modified by molecular events occurred during transcription and translation [12 ].
Molecular biomarkers in colorectal carcinoma
According to the EMA, a biomarker is defined as 'a measurable DNA and/or RNA characteristic that is an indicator of normal biologic processes, pathogenic processes and/or response to therapeutic or other interventions' [13 ]. Attending to their potential clinical application, biomarkers can be classified into prognostic biomarkers, when they indicate the future...