| Autor: |
Šitić, Sanda, Ramić, Snježana, Perić Balja, Melita, Starčević Božović, Angelina, Veliki Dalić, Irena, Milković Periša, Marija, Šarčević, Božena |
| Přispěvatelé: |
Krušlin, Božo, Mikuz, Gregor, Čupić, Hrvoje, Grabarević, Željko |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Popis: |
INTRODUCTION: Colorectal carcinoma (CRC) is the third most common malignancy worldwide. Survival depends on stage and grade with over 40% of metastatic disease and 5-year overall survival rate of 63%. Treatment options for CRC are surgery, chemotherapy and radiation therapy. The epidermal growth factor receptor (EGFR) was recognized as an important receptor that ini- tiates CRC progression via RAS-RAF-MAPK signaling pathway. Targeted therapy with monoclo- nal antibodies (cetuximab and panitumumab) have been developed to inhibit EGFR. Anti-EGFR therapy is ineffective in CRC with mutations in RAS genes because their proteins function down- stream of EGFR-induced cell signaling. KRAS gene mutations are detected in 35-54% of CRC, mainly in exon 2 (codons 12 and 13), and NRAS mutations are detected in 3-6% of CRCs. Prior anti-EGFR therapy, detection of KRAS mutations in exon 2 is bligatory. MATERIAL AND METHODS: KRAS mutations were detected in 90 cases of metastatic CRC. DNA was extracted from FFPE tissue samples and mutations were detected by Cobas® 4800 real-time PCR. In cases without KRAS mutation in exon 2, additional RAS testing was performed, using several IVD detection kits, designed to detect 28 mutations of KRAS and 25 mutations of NRAS gene. RESULTS: Out of 90 patients, 50 patients were male and 40 were female, with a median age of 60 years at the time of first diagnosis. Mutations were detected in 49 cases (54.4%) ; 47.8% in KRAS and 6.6% in NRAS gene. KRAS gene was mutated in 43 cases ; 35 in codon 12/13, 4 in codon 146 and 2 in codons 61 and 117. NRAS gene was mutated in 6 cases ; 3 in codon 12/13, 1 in codon 61 and 2 in codon 146. In male patients, KRAS was mutated in 56% and NRAS was mutated in 4% of cases, while in female patients, mutated KRAS was detected in 37.5% and NRAS was mutated in 10%. Patients with right-sided CRC were older (median age 68 years) and more often with mutations (75%) than patients with tumors localized in the left colon (median age of 58.5 years ; 53.5% RAS mutations). DISCUSSION: Recent studies have shown that anti-EGFR treatment is ineffective, not only in patients whose tumors have KRAS mutations in exon 2, but also in those patients who have other RAS mutations. Moreover, they report that NRAS-mutated CRC patients have better prognosis than those with KRAS mutations. They have not established the association of clinicopathological characteristics and RAS mutations status. CONCLUSION: Prior to the application of anti-EGFR therapy it is necessary to determine both KRAS and NRAS mutations status. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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