الفهرس 
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Abstract
According to GLOBOCAN 2020, lung cancer is the leading cause of cancer-related death, accounting for an estimated 1.8 million deaths. Non-small cell lung cancer (NSCLC) represents more than 80% to 85% of lung cancers of which approximately 40% are adenocarcinoma (ADC). The treatment of NSCLC tumors has relied heavily on targeting mutations in the kinase domain of the epidermal growth factor receptor (EGFR) gene, which is a vital gene that regulates cell activity; its mutation is associated with a decrease in EGFR tyrosine kinase (TK) activity, which is associated with late disease stage and poor progression of NSCLC.
Since 2004 and till now three generations of tyrosine kinase inhibitor have been developed, but unfortunately most of the patients who received any of these generation developed resistance. Transformation of small cell lung cancer and downstream gene mutations [Kristen rat sarcoma viral oncogene homolog (K-RAS) and v-raf murine sarcoma viral oncology homolog B (BRAF)] were discovered in patients with resistance. Codons 12/13 K-RAS mutations gene was described in approximately 20% of NSCLC/ADC.
This study determines the frequency and pattern (s) of EGFR and K-RAS mutations in NSCLC /ADC Egyptian patients and correlates the detected mutations to the patients’ relevant clinico-pathological data.
DNA was extracted and purified from the selected formalin-fixed, paraffin-embedded (FFPE) tissue blocks of 139 patients with NSCLC/ADC recruited from the National Cancer Institute (NCI) data clinics using the QIAamp DNA FFPE tissue kit (Qiagen, Germany). EGFR mutations were then detected on a Rotor-Gene Q MDx 5plex HRM instrument (Germany) using the Therascreen EGFR RGQ PCR kit (Qiagen, Germany). Each sample was subjected to PCR-RFLP (PCR with restriction fragmentation length polymorphism) analysis for PCR amplification of K-RAS gene codons 12 and 13.
The obtained results are summarised as follows:
• EGFR mutations were found in 31/139 (22.3%) of the cases, and were non-significantly more common in females than males and non-smokers than smokers.
• The most common detected mutations were exon 19 deletion and exon 21 point mutation, which accounted for 12.2% and 8.6% of all 139 samples, respectively. Only two cases (1.4%) had a mutation in exon 18 G719X.
• K-RAS mutations were discovered in 24/139 (17.3%) patients and were found to be non-significantly more common in smokers than non-smokers and in males rather than females.
• Nine patients (6.5%) had mutations in both genes (EGFR and K-RAS).
• EGFR and K-RAS mutations were significantly high with high grades. Also metastasis showed significance with EGFR mutations.
• The highest hazard ratio overall survival for both genes was found when K-RAS was the only mutant 10.77 (95% CI: 3.22-35.91), and when both gene was mutated the HR decreased to 6.87 (95% CI: 1.7-27.61). Meanwhile EGFR mutation was significantly correlated with better outcome having the least hazard ratio when it was the only mutant 3.31 (95% CI: 0.84-13.30).
In conclusion, mutations in EGFR and K-RAS are common in Egyptian patients with NSCLC/ADC (National Cancer Institute experience). Their incidences were found to be in between the Asian Pacific and Europeans. Also, their mutations are correlated with late disease stage and poor progression. As a result, they should be analysed in order to determine a better treatment method and predict survival outcomes.