[Relationship between EGFR and KRAS mutations and prognosis in Chinese patients with non-small cell lung cancer: a mutation analysis with real-time polymerase chain reaction using scorpion amplification refractory mutation system]

Zhonghua Bing Li Xue Za Zhi. 2012 Oct;41(10):652-6. doi: 10.3760/cma.j.issn.0529-5807.2012.10.002.
[Article in Chinese]

Abstract

Objective: To investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC), and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency.

Methods: EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010, and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study.

Results: EGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC, in which three types of EGFR gene mutations were found: deletion in exon 19, exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations. There were 29(24.2%) patients with EGFR exon 19 deletion, 14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients. All the mutations were single point mutations, and no multiple points mutations detected. EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma (P = 0.009). EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P = 0.014, P = 0.001, respectively) in NSCLC patients. EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P = 0.008, P = 0.018, respectively). There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients. Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients. There were four types of KRAS gene mutations detected: KRAS Gly12Ala (GGT > GCT), KRAS Gly12Arg (GGT > CGT), KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT). There were 4 patients with Cys mutation, 2 with Arg mutation, 2 with Val mutation and 1 with multiple points mutation of both Cys and Arg in exon 12. No relationship was found between KRAS mutation and clinicopathological feature either in NSCLC or in adenocarcinoma. Prognosis was worse in patients with KRAS mutation than in wild-type patients (P = 0.008). No patient with both EGFR and KRAS mutation was detected.

Conclusions: EGFR mutation rate is related with gender, smoking history and pathological type in NSCLC patients, and is also related with differentiation and smoking history in adenocarcinoma patients. And prognosis is worse in patients with KRAS mutation than that with wild type.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Bronchiolo-Alveolar / genetics
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • ErbB Receptors / genetics*
  • Exons
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Sex Factors
  • Smoking
  • Survival Rate
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins