Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer
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Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus not accurately reveal the EGFR expression. In addition, EGFR expression may also change during chemotherapy. The current study investigates the magnitude of these two issues.
Materials and methods
EGFR expression in diagnostic biopsies and resection specimen was compared in 53 NSCLC patients stage T1-4N0-1M0 treated with surgery without preceding chemotherapy (OP group), and 65 NSCLC patients stage T1-3N0-2M0 (NAC group) treated with preoperative carboplatin and paclitaxel in order to evaluate the discordance of EGFR expression between samples.
Discordance between tumors dichotomized according to EGFR expression (high: H-score ≥200; low: H-score <200) in diagnostic biopsies and immediate resection specimens was 25 % in the OP group and 33 % in the NAC group (p = 0.628). Five (9 %) of primary tumors in the OP group and 4 (13 %) in the NAC group had increased EGFR expression in the resection specimens as compared to the diagnostic biopsies (p = 0.583). A decrease in EGFR expression was observed in 6 (11 %) in the OP group and 7 (23 %) in the NAC group (p = 0.148).
EGFR expression in 25 % of diagnostic biopsies may potentially not be accurate compared to the prevailing pattern in the whole tumor based on the larger resection specimens. This may potentially be an obstacle for proper use of antibodies targeting the EGFR in NSCLC. EGFR expression does, however, not change significantly during paclitaxel and carboplatin and rebiopsies in order to decide on anti-EGFR antibody therapy following chemotherapy do not seem warranted.
KeywordsNSCLC Chemotherapy Biomarker EGFR Heterogeneity
We thank Camilla Cordua Mortensen, Heidi Ugleholdt, and Lone Svendstrup for expert technical assistance. This study was supported by the Danish Cancer Research Foundation, Arvid Nillsons Foundation, Torben and Alice Frimodts Foundation, Aase and Ejnar Danielsens Foundation, Eva and Henry Fraenkels Foundation, The Danish Research Foundation, Snedkermester Sophus Jacobsen and Hustru Astrid Jacobsens Foundation, The Foundation for the Promotion of Medical Cancer Treatment, and The Research Foundation of the Department of Oncology, Rigshospitalet.
Conflict of interest
The authors Jan Nyrop Jakobsen and Eric Santoni-Rugiu did not declare any conflicts of interest, and Jens Benn Sørensen received speaker’s fee from Roche.
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