A single-centre experience with broader predictive testing for anti-EGFR therapy in metastatic colorectal cancer patients

Konference: 2015 11. sympózium molekulovej patológie s medzinárodnou účasťou a Martinské dni nelekárskych pracovníkov v patológii

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie


Číslo abstraktu: 044

Autoři: Mgr. Nikola Hájková; RNDr. Ivana Tichá, Ph.D.; Prof. MUDr. Pavel Dundr, Ph.D.

Objective: Since late 2013 the evidence of wild type KRAS and NRAS in exons 2 - 4 have been required before initiating anti-EGFR treatment (cetuximab and panitumumab) in Czech metastatic colorectal cancer (mCRC) patients. The aim of this report is to show the importance of inclussion of exon 4 of KRAS and NRAS exons 2 4 into predictive testing compare with previous testing only in KRAS exons 2 3.

Methods: DNA from 231 formalin-fixed paraffin-embedded tissue, collected between January 2014 March 2015, was isolated using QIAamp DNA Mini Kit or cobas DNA Sample Preparation Kit. Samples with≥ 10% of tumour cells were examined. Macro-/micro-disection was applied when needed. Techniques based on real-time PCR and melting analysis (Diacarta;

LightMix; Cobas) or multiplex PCR followed by hybridization (Strip Assay,Vienna Lab) were applied.

Results: KRAS mutations in exons 2 and 3 were in 35,1 % (81/231) patients. Broader testing identified additional 25,3 % (38/150) RAS mutations: 10,7 % (16/150) in KRAS exon 4, 8,7 % (13/150) and 6 % (9/150) in NRAS exon 2 and 3, respectively.

Conclusion: Extension of RAS testing revealed another 16,5 % (38/231) of mCRC carriers of RAS mutation who are unlikely to benefit from anti-EGFR treatment. Inclusion of other genetic factors related to prognosis and/or prediction is necessary to improve targeted therapy.

This work was supported by Charles University in Prague, project PRVOUK-P27/LF1/1.

Datum přednesení příspěvku: 5. 6. 2016