Analysis of EGFR pathway mediators in KRAS wild-type primary tumors is not representative of their status in related metastases.

Abstract

3589 Background: KRAS mutated CRC patients are nonresponsive to anti-EGFR. In contrast, the clinical benefit of KRAS wild type is uncertain and needs further studies. Our retrospective study compared the status of the most relevant EGFR pathway downstream regulators between primary tumors and related metastases of KRAS wild type patients. Methods: One hundred and seventeen pairs of primaries and metastases from patients diagnosed with CRC were tested for KRAS mutated status. Wild type KRAS pairs were further analyzed downstream for EGFR mediators and for EGFR itself. Pair concordance and impact of clinicopathological variables was analyzed. Patients were anti-EGFR therapy naive. Results: The level of concordance in the presence of KRAS mutations was 92% between the primary tumor and the related metastases. KRAS wild type pairs were analyzed for BRAF and PI3KCA mutational status and for EGFR and pAKT expression and PTEN lost in patients pairs and levels of concordances were 100%, 94%, 61%, 53% and 73% respectively. Of the 61% KRAS wild type patients, only 18% showed complete concordance between the primary tumor and the related metastases for the rest of the five markers analyzed. Thus, 82% of KRAS wild type pairs showed a different EGFR pathway status between the primary tumor and the related metastasis. Conclusions: In this most extensive study to date of tumoral pairs, results show that for 82% of the KRAS wild type patients, the analysis of the primary tumor is not representative of the related metastases, suggesting the need for rebiopsy of the metastases to adjust the anti-EGFR therapy predictive value of some EGFR mediators. No significant financial relationships to disclose.