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

Abstract

The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC) among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS) and disease-free survival (DFS) in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230), which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001). Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4) and in lymph node (LN) metastases (N1/N2) (P=0.029 and P=0.010, respectively). The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001) and in metastatic CRC that had infiltrated more deeply (T3, T4) (P=0.034). In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035). Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively). In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029). The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and the KRAS mutation is correlated with a shorter OS and DFS, as patients with wild-type KRAS who received cetuximab experienced a longer DFS.

Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

“…Other studies found no significant correlation with gender, ethnicity, age, tumor differentiation, histological type, and the presence of distant metastases. However, they found in patients with metastatic disease, KRAS mutations were more common in individuals older than 65 years (p = 0.035) [16]. Regarding MSI status, 57.9% of our patients had MSI-H CRC which was reported as a factor associated with improved prognosis [17].…”

“…Other studies found that KRAS mutation was more likely to be noted in male subjects (p = 0.010) [15]. However, in other reports, an even distribution of KRAS mutations has been described in both genders [16]. There was no significant difference in the clinicopathological features between KRAS mutant and KRAS wild patients except for patient age where KRAS mutation was detected in older individuals with p value = 0.003.…”

Biomarker concordance between primary colorectal cancer and its metastases

“…61 studies including 3565 patient samples were included. Median biomarker concordance for KRAS ( n = 50) was 93.7% [[67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]], NRAS ( n = 11) was 100% [[90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]], BRAF ( n = 22) was 99.4% [[80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]], and PIK3CA ( n = 17) was 93% [[42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59],…”

“…Concordance in individual biomarker status in patients with mCRC was reported in a range of oncogenes and tumour suppressor genes. The median reported concordance was 93.7% (range 67–100) for KRAS ( n = 50) [24,[44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93]], 99.4% (range 80–100) for BRAF ( n = 22) [44,45,48,49,54,60,61,[63], [64], [65],[67], [68], [69],71,[73], [74], [75], [76],79,80,83,86], 93% (range 42–100) for PIK3CA ( n = 17) [44,[48], [49], [50], [51],53,54,[58], [59], [60],…”

“…27 studies analysed biomarker concordance separately within these metastatic sites as displayed in Table 4 , thus allowing comparison between metastatic location and the possible impact on concordance. Of these studies, 21 gave concordance data specific to liver metastases [ [44] , [45] , [46] , [49] , [50] , [51] , 53 , 56 , 61 , [63] , [64] , [65] , 69 , 70 , 72 , 77 , [80] , [81] , [82] , 94 , 100 ], 11 for lung metastases [ 38 , 42 , 49 , 59 , 60 , 65 , 68 , [84] , [85] , [86] , [87] ] and 12 for lymph nodes [ 46 , 47 , 49 , 52 , 57 , 60 , 61 , 67 , 68 , 75 , 84 , 87 ]. Only two studies provided separate concordance for peritoneal metastases and likewise only single studies for ovarian and bone metastases were available, with most studies grouping these with other metastatic sites [ 45 , 53 , 63 , 89 ].…”