Balkan Journal of Medical Genetics

THE FREQUENCY OF EGFR AND KRAS MUTATIONS IN THE TURKISH POPULATION WITH NON-SMALL CELL LUNG CANCER AND THEIR RESPONSE TO ERLOTINIB THERAPY
Demiray A, Yaren A, Karagenç N, Bir F, Demiray AG, Karagür ER, Tokgün O, Elmas L, Akça H, https://orcid.org/0000-0002-3343-0184.
*Corresponding Author: Professor Dr. Hakan Akça, Cancer Research Center, Pamukkale University, 11 University Street, Denizli Turkey. E-mail: hakca@pau.edu.tr (primary), hakanakca@yahoo.com
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RESULTS

Patient Profiles. We conducted this study on paraffin- embedded tissues of 300 consecutive patients with NSCLC from January 2010 through January 2014. In the 300 patients with NSCLC, 230 (76.7%) patients had advanced disease, 62 (20.7%) of these patients were female, 238 (79.3%) were male. Histopathologically, there were 62 squamous and 228 adenocarcinoma NSCLC patients. The median age of the patients was 62 (range 37-82), 233 (74.3%) had a history of smoking. The patient characteristics are summarized in Table 1. EGFR Mutations Profiles. We detected EGFR mutations in 97 patients out of 300 patients, 30 of which were female and 67 were male patients. Histopathologically, 13 were squamous type 77 adenocarcinoma, while seven were in other subtypes. In terms of age, 50 patients were over 62 years old, 47 patients were less than 62, and 59 of them are smokers. The EGFR mutations were found to be statistically significant in females, non smokers and adenocarcinoma patients. Eighteen patients were in early stages (I-IIIA), while 79 patients were in advanced stages (IIIB-IV), considering progression [9] (Table 2). We detected 53.5% EGFR mutations in exon 19 [Table 3(A)]. KRAS Mutation Profiles. Seventy-five of 300 patients have KRAS mutations, 12 of which were females, 63 were males. Histopathologically, 18 patients have squamous type NSCLC, while 55 have adenocarcinoma and two were in other subtypes. Thirty-two patients were older than 62 and 58 patients were smokers. Sixteen patients were in early stages and 59 patients were in advanced stages of cancer (Table 2). We found no statistically significant differences between KRAS mutations and age, gender, smoking, stage of the cancer. We detected both EGFR-KRAS mutations in 20 patients, four females and 16 male patients. Histopathologically, two of them were squamous, 16 were adenocarcinoma and two were in other types. Two were in early stage, 18 were in advanced stages, 13 of them were older than 62. Eleven of them are smokers, while nine are not. Detailed information is given in Table 2. Survival Rates of Patients with EGFR-KRAS Mutations. Fifty-nine patients who had either EGFR mutations or both EGFR and KRAS mutations, received erlotinib therapy. We showed that survival rates of patients who received EGFR-TKI therapy was significantly higher than patients with EGFR mutations who did not receive erlotinib therapy [Figure 1(A) and 1(B)]. Twenty patients who have EGFR-KRAS mutations and were not treated with erlotinib, had the lowest survival rate (34 ± 16 weeks) (p 0.0007) [Figure 2(B)]. Patients with both mutations and who received erlotinib therapy, had a survival rate of 98 ± 16 weeks [Figure 2(B)]. Patients who had only the EGFR mutation and were treated with erlotinib, had a survival rate of 161 ± 30 weeks [Figure 2(A)], and those who did not receive erlotinib therapy, had a survival rate of 90 ± 13 weeks [Figure 2(A)]. The overall survival rate patients treated with EGFRTKI without progression was also found to be significantly higher. Patients who were treated with EGFR-TKI: 288 ± 11 and those who were not: 119 ± 11 weeks (p 0.004) [Figure 1(A)]. Overall survival rates were 126 ± 11 in patients with EGFR mutations and 121 ± 9 weeks in other patients (p 0.266) [Figure 1(B)]. We observed, that patients who have both EGFR and KRAS mutations, have the lowest overall survival rate and erlotinib therapy increased the survival rate in patients who have both mutations, while progression-free survival rates in patients treated with erlotinib were 32 ± 5 weeks, these rates were 33 ± 3 weeks in patients who were not treated with erlotinib (p 0.755). KRAS mutation 100 ± 4, without mutation 131 ± 11 weeks, p 0.038, and without a progression survival rate was not statistically significant (KRAS mutations 31 ± 5, without KRAS mutation 33 ± 3 weeks, p 0.0807).

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