Detection and Quantitation of EGFR Gene Copy Number/Amplification by FISH in Non-Small Cell Lung Cancer (NSCLC) A Comparative Study with IHC Stains in 537 Cases
S Chopra, B Shahbahrami, T Cheng, M Gu. Oncotech Inc., Tustin, CA; University of California Irvine Medical Center, Orange, CA
Background: Lung cancer is the most frequently diagnosed malignancy and the most common cause of cancer related mortality worldwide. Despite early diagnosis and improvements in therapy, the overall 5-year survival rate of NSCLC is 15%. NSCLC frequently expresses EGFR and this led to the development of Iressa and Tarceva, small molecule EGFR tyrosine kinase inhibitors. However, conflicting results have been reported in correlation between an objective clinical response to TKIs and EGFR testing results due to different tests being used.
Design: FISH studies for NSCLC performed at Oncotech Inc. with IHC from 11/2005 to 4/2007 were retrospectively retrieved. H&E slides were reviewed for histologic classification including adenocarcinoma (ADE), bronchioloalveolar carcinoma (BA), poorly differentiated carcinoma (PDCA), and squamous carcinoma (SQC). The IHC stains were interpreted as negative (0, 1+) and positive (2+, and 3+). FISH results were categorized as negative (disomy, low trisomy, high trisomy, and low polysomy) and positive (high polysomy and gene amplification).
Results: Five hundred and thirty-seven patients were identified. EGFR was positive by IHC in 420 (78.2%) cases and was positive by FISH in 226 (42.1%) cases. The comparison of the results from these two methods was summarized in Table 1.
EGFR expression results by IHC and comparison with FISH
|FISH Positive||FISH Negative|
|IHC Positive (N=420)||194 (46.2%)||226 (53.8%)|
|IHC Negative (N=117)||32 (27.4%)||85 (72.6%)|
The histologic correlation of 537 cases was summarized in Table 2.
Distribution of Histology for IHC and FISH Studies
|Histology||Cases (N=537)||Positive by IHC (N=420)||Positive by FISH (N=226)|
|ADE||263||191 (72.6%)||110 (41.8%)|
|BA||14||6 (42.9%)||3 (21.4%)|
|PDCA||135||101 (74.8)||57 (42.2%)|
|SQC||125||112 (89.6%)||56 (44.8%)|
Conclusions: IHC tends to have higher positive rates for EGFR expression, particularly for squamous carcinoma. The EGFR expression correlates with EGFR gene copy number abnormalities in half of the NSCLCs. EGFR gene copy number alterations do not always correlate with EGFR expression level. Other underlying mechanisms for EGFR regulation exist in NSCLC. The role of current EGFR testing for guiding target therapy therefore remains to be investigated.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 242, Wednesday Afternoon