Mutations in K-ras and Epidermal Growth Factor Receptor Expression in Korean Patients With Stages III and IV Colorectal Cancer

Abstract

K-Ras somatic mutations in advanced colorectal cancer (CRC) can predict resistance to mAbs that target the epidermal growth factor receptor (EGFR). The relationships between K-ras mutations and the EGFR status have not yet been examined, especially in Korean patients. A total of 82 colorectal tumors (stage III-IV) were analyzed. K-Ras mutations at codons 12 and 13 were detected by polymerase chain reaction-single strand conformational polymorphism. The EGFR expressions were examined by immunohistochemistry, and these were graded according to a modified EGFR expression scoring system. The relationships between the patients' characteristics and the survival time and the gene mutation status were analyzed. The EGFR expression was positive in 69 patients (84.1%) and negative in 13 patients (15.9%). The K-ras mutation rate was 35.4%. In all, 20 (68.9%) cases were mutated at codon 12 and 9 (31.1%) cases were mutated at codon 13. No relationship was observed between the EGFR status and K-ras mutation. The median overall survival (OS) was 68.1 months. There was no difference between the K-ras mutant group and the wild type group for overall survival (30.3% vs 21.0%, respectively, at 36 months, P = .777). K-ras mutation and the EGFR status were not independent prognostic factors for OS (P = .105 and P = .499, respectively). For the Korean patients with CRC, the rate of an EGFR protein expression was greater than that for the patients in Western countries, and the rate of K-ras mutations was lower than that for patients in Western countries. This study found no correlation between the EGFR status and K-ras mutations in colorectal tumors.

Kras Mutation Frequency and Spectrum in Colorectal Cancer: Correlation With the Tumor Localization in Kazakhstani Population

“…Of the 332 CRC patients included in the study, 149 (44.9%) had mt-KRAS, and 183 (55.1%) had wt-KRAS. Our results correspond to the results obtained in extensive multicenter studies which confirm the 30-50% mutation frequency of KRAS in colon tumors [1,3,[5][6][7]. Thus, our results on the frequency of KRAS gene mutation are consistent with data published by other researchers.…”

“…Still, there is evidence that KRAS gene mutates more often in rectal tumors than in tumors in the overlying colon. Some researchers have revealed the relation of the KRAS gene mutation in codon 13 with the stage of the tumor process [3][4][5][6].…”

RAS status in Korean patients with stage III and IV colorectal cancer

“…1 (Table 4) [20][21][22][23][24]. The low frequency in our data may be explained as suggested by Bazan et al [25], a wide range might be due to several factors such as the different laboratory techniques used for analyzing the expanded RAS mutations, namely BEAMing, pyrosequencing, and dideoxy sequencing (Table 4), different tumor storage methods (fresh frozen tissue versus paraffin-embedded blocks), tumoral heterogeneity and the histologic characteristics of the patient included in the study, such as the histopathological staging, the tumor differentiation, and tumor location [1]. Another reason that might contribute to such discrepancies may be the germline genetic variation associated with ethnicity predisposes an individual to RAS gene mutations highlighting the need to investigate cancer genomes from patients of all ethnicities across the world.…”

“…Colorectal cancer is the third most common frequent cancer among men and the second most frequent cancer among women worldwide [1]. In Korea, incidence of colorectal cancer has been increasing during the past decade [2].…”

Comparison of HER2 expression between primary colorectal cancer and their corresponding metastases

“…The PCR products were finally purified on Centri‐Sep Spin Columns (Applied Biosystems) and subsequently run on an ABI Prism 310 automatic sequencer (Applied Biosystems). The data were analyzed using Sequencing Analysis 5.2 Software (Applied Biosystems) .…”