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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Concordance between epidermal growth factor receptor status in primary non-small-cell lung cancer and metastases: a
Stefan B Watzka1, Irene Rauscher-Pötsch, Patrick Nierlich
1Karl Landsteiner Institute of Thoracic Oncology, Division of Thoracic Surgery, Otto Wagner Hospital, Sanatoriumstrasse 2, 1140 Vienna, Austria. s.watzka@utanet.at
Objectives:
Epidermal growth factor receptor (EGFR)-targeted therapies are a valid therapeutic option for advanced non-small-cell lung cancer (NSCLC), but unequivocally recognised predictive factors for therapeutic response are lacking. However, intrinsic resistance might occur due to loss of EGFR expression during the course of the disease or its treatment.
Methods:
Paraffin-embedded tissue from cases with metastatic NSCLC obtained at autopsy was retrieved from our archive. Specimens of primary tumour (n=39; 64% adenocarcinoma) and of all corresponding metastases (n=70) were immunohistochemically stained for EGFR expression. Two observers independently scored staining intensity and evaluated the percentage of positively stained cells. Identical staining intensity and < or = 10% difference in number of stained cells were defined as perfect concordance; and one-increment difference in staining intensity and less than 30% difference in number of stained cells were defined as good concordance.
Results:
Twenty-seven out of 39 primary tumours (69%) were EGFR-positive on immunohistochemistry (IHC), with 12/27 (44%) of positive tumours exhibiting intense or moderate EGFR expression. The median number of EGFR-expressing cells in primary tumours was 50% (range 0-100%). Overall Spearman's rank correlations for staining intensity and percentage of positively stained cells between primary tumours and paired metastases were 0.78 (p<0.001) and 0.60 (p<0.001), respectively. Perfect concordance was observed in 51% (20/39) and good concordance in 18% (7/39) of corresponding pairs, respectively, whereas 9/12 metastases showing discordant staining with their corresponding primary tumours had lacked EGFR expression.
Conclusions:
In most NSCLCs, EGFR status of primary tumours correlates with EGFR status of corresponding metastases. Hence, loss of EGFR expression is unlikely during disease progression, local or non-EGFR-targeting systemic treatment.
