KRAS mutational concordance between primary and metastatic colorectal adenocarcinoma

Abstract

KRAS mutation analysis is commonly performed on tissue samples obtained from primary colorectal cancers (CRCs). The metastatic lesions of CRC are usually considered as qualitatively similar or even identical to the primary tumors. The aim of this study was to evaluate the spectrum and distribution of KRAS mutations in a large collection of CRCs, while also evaluating the concordance of primary and metastatic lesions among available paired specimens from the same patients. A total of 729 patients with histologically confirmed advanced CRC at the University Hospital and Local Health Unit (Sassari, Italy) were included. Clinical and pathological features were obtained from medical records and/or pathology reports. Formalin-fixed, paraffin-embedded tissue samples were used for mutation analysis. Genomic DNA was isolated using a standard protocol; the coding sequence and splice junctions of exons 2 and 3 in the KRAS gene were screened by direct automated sequencing. Overall, 219 (30%) KRAS mutations were found; 208 (30.1%) were identified in the 690 primary tumors and 11 (28.2%) in the 39 metastatic tissue samples. Among the 31 (4.3%) patients who had paired samples of primary CRC and synchronous or asynchronous metastases, 28 (90.3%) showed consistent mutation patterns between the primary tumors and metastatic lesions. In one case, an additive mutation (Q61L) was found in the metastatic tissue, while two other discrepant cases exhibited a different mutation distribution; Q61H in the primitive lesion and G13V in the metastatic lesion in one case, and a mutated primary tumor (Q61L) and wild-type metastasis in another case. The results of this study confirm that a high concordance exists between the results of KRAS mutation analysis performed in primitive and metastatic CRCs; independent subclones may be generated in a limited amount of patients.

Association between clinicopathological features and survival in patients with primary and paired metastatic colorectal cancer and <em>KRAS</em> mutation

“…For example, Siyar Ekinci et al found that the KRAS mutation rate is inconsistent between liver or lung metastases and primary tumors; both the primary tumor mutant and paired metastases wild-type also have primary tumor wild-type and paired metastases mutant 21,23. Moreover, KRAS gene consistency has been reported between primary tumors and metastases, especially non-metastatic LNs 16. In our study, the KRAS gene status was not consistent between primary tumors and LN metastases but identical between primary tumors and liver or lung metastases.…”

Concordant analysis of KRAS, BRAF, PIK3CA mutations and PTEN expression between primary colorectal cancer and matched metastases

“…Mutation status concordance was reported in 43 studies for KRAS 4 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 , in 16 studies for BRAF 7 13 14 15 16 17 18 24 25 26 27 33 34 41 43 48 , in 9 studies for PIK3CA 13 14 15 18 25 27 34 48 49 and in 8 studies for PTEN 7 13 17 31 32 34 47 48 . The majority of studies (40/43) tested the KRAS mutations on codons 12 and 13 4 7 8 …”

“…Searching of ASCO did not identify any further eligible studies, while reference list checking of reviews and included studies identified 2 additional studies. In total, 46 relevant studies 4 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 were identified. Details are presented in figure 1 .…”

“…Case-control study design was avoided in 42 studies 4 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 36 37 38 39 41 42 43 46 47 48 49 50 51 while the study design was unclear or not reported in the remaining 4 studies 35 40 44 45 . Only 2 studies 7 37 (2/46) reported assessor blinding, whereas the rest 4 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 38 39 40 ...…”

High concordance rate of KRAS/BRAF mutations and MSI-H between primary colorectal cancer and corresponding metastases

“…KRAS mutation is recognized as an early event in colorectal carcinogenesis (20,21). Therefore, concordance of KRAS mutation status between primary CRC and corresponding metastases should be expected, and previous studies demonstrated high concordance rate (22)(23)(24). Nevertheless, some other studies reported discordance of KRAS mutation status between primary CRC and corresponding metastases.…”