ASSESSING GENETIC MUTATIONS OF SOME CANCERS AT BACH MAI HOSPITAL

1. ASSESSING GENETIC MUTATIONS OF SOME CANCERS AT BACH MAI HOSPITAL Mai Trọng Khoa, Phạm Cẩm Phương et al., The Nuclear Medicine and Oncology Center, Bạch Mai hospital

2. Top 10 cancers in Vietnam

3. Signal transduction in cancers

4. Biomarkers in targeted therapy

5. Study objectives • To determine the mutation of EGFR, KRAS, NRAS, BRAF genes in patients with non-small cell lung cancer, colorectal cancer, thyroid cancer and • To evaluate relation of different variables to its frequency

6. Subjects and methods • Patients: 1082 patients with non-small cell lung cancer, colorectal cancer and thyroid cancer were identified their gene EGFR, KRAS, NRAS, BRAF at Bach Mai hospital, Nov/2014 – Sep/2017 • Methods: Prospective study • Gather patient information in a unified form. • Detection of EGFR, KRAS, NRAS, BRAF gene mutations from formalin-paraffin-embedded tissue (FFPE) • Data processing: using SPSS 19.0 software

7. Subjects and methods • Gene mutation detection: sample deparaffinization Elution Lysis Washing

8. EGFR gene mutation frequency n = 391 n = 922

9. Relation of different variables to EGFR mutation frequency < 50 41,1% Age 50 – 64 41,8% ≥ 65 39,8% Male 33,6% Gender Female 56,0% 0% 10% 20% 30% 40% 50% 60% • Rates of EGFR mutation in patients aged 50-64 were higher than those in the 2 groups (p = 0.476), mean age 60.2 years • The EGFR mutation rate in the female patient group was 1.67 times higher in the male patient group (p <0.0001)

10. Relation of different variables to EGFR mutation frequency 30,0% Smoker 57,0% Non-smoker Smoking history Male/ Smoker 30,0% Male/ Non-smoker 55,8% 0% 10% 20% 30% 40% 50% 60% • Rates of EGFR mutations in the non-smoker group were higher than those who smoked (p <0.0001) • Male: The incidence of EGFR mutations in the non-smoker group was higher (p = 0.013)

11. Relation of different variables to EGFR mutation frequency I 43,6% Stage II 45,1% III 39,3% IV 41,1% Pathology 42,1% adenocarcinoma Others 23,9% 0% 10% 20% 30% 40% 50% 60% • Rates of EGFR mutation in patients with stage I-II was higher than in stage III-IV (p = 0.757) • Rates of EGFR mutation in patients with adenocarcinoma were higher than those of other types (p = 0.015).

12. Relation of different variables to EGFR mutation frequency lung tumor 43,3% Location 35,2% metastases ‘ pleural fluid 32,4% surgery 34,5% Sampling method biopsy 43,0% anesthetic 32,4% 0% 10% 20% 30% 40% 50% 60% • The rate of EGFR mutation in the lung tumors was higher in the than in the metastatic or pleural fluid (p = 0.01). • The rate of EGFR mutation in the biopsy was higher than that of the surgical or anesthetic group (p = 0.121)

13. KRAS, NRAS gene mutation frequency K K K K K K K K K K K K K KRAS: 38,7% (24) N N N N N K NRAS: 11,3% (57) Wild type (50%)

14. KRAS, NRAS gene mutation frequency • KRAS mutations were detected in the majority of codons (22 patients), 1 mutation in 146 codons and no mutations in the 61 codon • NRAS gene, mutations in the codon 12-13 predominate with (5/7 patients). One patient carried two mutants

15. Relation of different variables to KRAS,NRAS mutation frequency % % 38,9% 38,5% 30,8% 27,8% 22,2% 16,7% 7,7% 3,8% Gender Male Female < 60 ≥ 60 Age NRAS mutation KRAS mutation

16. Relation of different variables to KRAS,NRAS mutation frequency % % 41,7% 75,0% 31,3% 16,7% 30,0% 9,4% 12,5% 0% Others Adenocarcinoma I-II III-IV Stage Histopathology NRAS mutation KRAS mutation

17. Relation of different variables to KRAS,NRAS mutation frequency % % 37,1% 34,6% 33,3% 22,2% 22,2% 15,4% 8,6% 5,6% Sampling method Colon Biopsy Surgery Rectal Tumor location NRAS mutation KRAS mutation

18. Relation of different variables to KRAS,NRAS mutation frequency % % 46,2% 36,1% 31,8% CEA 29,0% CA 19-9 18,2% 16,1% 4,5% 0% Normal Elevated Elevated Normal NRAS mutation KRAS mutation The correlation between KRAS, NRAS mutations were not depend on characteristics such as age, gender, method of sampling, tumor location and histopathology.

19. BRAF gene mutation frequency • Relation of BRAF mutation frequency with age and gender BRAF wild type BRAF mutation • The majority of patients were female, 86.9% (172/198) • The average age for both men and women were 45.1 years

20. Relation of different variables to BRAF mutation frequency • BRAF mutation frequency and histophathology • BRAF mutation was found in thyroid tumor (75.2%), lymph node (80.8%) and metastasis (66.8%) respectively. • BRAF mutation was detected in papillary thyroid cancer (76.6%), follicular thyroid cancer (40%). follicular-papillary thyroid cancer (80%)

21. Relation of different variables to BRAF mutation frequency • BRAF mutation frequency and Staging, TNM BRAF mutation were not depend on the stage of disease , TNM staging

22. Conclusions • The EGFR gene mutation rate was 40.9%, the most common of which was on exon 19 (56.5%) and L858R, L861Q on exon 21 (36.3%). The T790M mutation on exon 20 associated with TKI resistance was only about 2.6%. • KRAS gene mutations were detected in 24/62 patients (38.7%), in which the common mutation was G12A on exon 2 (14 patients). NRAS gene mutations were detected in 7 patients (11.3%). One patient carried two mutations of KRAS, NRAS. • BRAF gene mutations were detected in 150/198 patients (75.8%), with all mutations in the codon 600 (V600E). • Genetic mutation testing is needed for clinicians to choose the best treatment option for cancer patients.

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