Concordance between epidermal growth factor receptor status in primary non-small-cell lung cancer and metastases: a post-mortem study.
OBJECTIVE
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.
Watzka
Stefan B
SB
Karl Landsteiner Institute of Thoracic Oncology, Division of Thoracic Surgery, Otto Wagner Hospital, Sanatoriumstrasse 2, 1140 Vienna, Austria. s.watzka@utanet.at
Rauscher-Pötsch
Irene
I
Nierlich
Patrick
P
Setinek
Ulrike
U
Köstler
Wolfgang J
WJ
Pötschger
Ulrike
U
Müller
Michael R
MR
Attems
Johannes
J
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000556:secondary* / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D066246:ErbB Receptors