Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations

Concordance of Predictive Markers for EGFR Inhibitors in Primary Tumors and Metastases in Colorectal Cancer: A Review

“…All studies tested for mutations in codon 12 and 13, except for Oudejans et al [56], who also tested for mutations in codon 61, and Suchy et al [42], who tested only for mutations in codon 12. Most authors reported codon 12 and 13 mutations in a ratio as would be expected according to the literature (i.e., approximately 80% in codon 12 and 20% in codon 13 when testing only codon 12 and 13); however, two reported relatively more codon 13 mutations [53,55] and two reported codon 13 mutations in Ͻ10% of cases [43,56].…”

“…Possible explanations according to the literature are acquirement of mutations during or after metastasizing, false-negative and false-positive test results, and heterogeneity of CRC tumors. Late occurrence of mutations, as suggested by Albanese et al [53] and Zauber et al [43], is a questionable explanation because KRAS mutations have been proven to be an early step in tumorigenesis [33,61,62]. False-negative and false-positive test results could also be an explanation for discordance.…”

“…However, only a minority of the studies reported in this review used techniques other than sequencing. Additionally, most studies on concordance have carefully reviewed the quality and tumor content of the samples included in their analysis, and some studies performed sequencing twice, starting from different amplification reactions [28,31,53], whereas others had two independent observers to determine KRAS status [50,52], or re-evaluated their results using pyrosequencing [54]. Therefore, although it is possible that a small number of the discordant cases are a result of poor quality testing techniques, false test results are not likely to explain the discordant cases in the majority of these studies.…”

“…Five studies found a concordance rate of 100% [39 -43], and in 10 additional studies the concordance rate was Ն90% [28, 30, 44 -51]. Five of the 21 studies reported concordance rates Ͻ85% [31,[52][53][54][55], with 76% being the lowest rate reported [54]. The overall concordance rate of the studies reported in Table 1 is 93%.…”

Cancer Stem Cells in Tumor Heterogeneity

“…Intriguingly, although many reports at least partially support the prediction of the clonal evolution theory (Fujii et al, 1996;Kuukasjarvi et al, 1997;Jones et al, 2008), several of the studies performed to date report remarkably diverging patterns of genetic alterations in primary tumors as compared to metastases from the same patient (Albanese et al, 2004;Katona et al, 2007;Artale et al, 2008;Kalikaki et al, 2008).…”