Immunohistochemistry with Mutation Specific Antibodies Detecting the Status of EGFR Mutations in Non-Small-Cell Lung Cancer
D Li, S Chen, C Hu, Y Lei, J Yu. Second Xiangya Hospital, Central South University, Changsha, China; Hunan Cancer Hospital, Changsha, China; Second Xiangya Hospital, Changsha, China; Hunan Province People's Hospital, Changsha, China; Cell Signaling Technology, Danvers, MA
Background: The association between EGFR mutations and response to EGFR tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer(NSCLC) has been consistently confirmed in a number of studies. Deletions in exon 19 and the L858R substitution in exon 21, accounting for approximately 90% of all EGFR mutations, are the best characterized sensitizing mutations in adenocarcinoma (AC). This study was designed to evaluate immunohistochemistry (IHC) with mutation specific antibodies to detect mutant EGFR proteins in NSCLC for patient selection to TKI therapy.
Design: We have screened 140 cases of NSCLC patient tumor samples, which included 90 cases of AC and 50 cases of SCC, by IHC using total EGFR antibody and exon 19 delE746_A750 and L858R mutation specific antibodies. The result was confirmed by direct DNA sequencing. In addition, we compared patient response to TKIs with the IHC staining result in 32 patients who were treated by TKI prior the screening.
Results: 10 cases were positively stained by EGFR and exon 19 delE746_A750 specific antibodies. 9 cases were positively stained by EGFR and L858R specific antibodies. Squencing found 24 cases with EGFR mutations. 14 cases were exon 19 deletions (10 type I and 4 other subtypes). 10 were L858R. All positive cases were from AC. All IHC positive cases were confirmed by DNA sequencing, but the rest 5 DNA sequencing positive cases were negatively stained by IHC (1 exon 19 delE746_A750, 3 other subtypes deletion and 1 L858R mutation). The specificity of IHC is 100% and sensitivity is 79.2%. 32 advanced disease cases were treated by Iressa until disease progression. In three month following up: 1 complete response (CR), 8 partial response (PR), 2 stable disease (SD), 21 progression of disease (PD). The total effective rate (CR+PR) was 28.1%, disease control rate (CR+PR+SD) was 34.4%. 9 of the 32 cases (28.1%) were IHC positive. 1 CR, 7 PR, 1 SD. Total effective rate (CR+PR) was 88.9% and disease control rate (CR+PR+SD) was 100.0%.
Conclusions: IHC with mutation specific antibodies to detect mutant EGFR proteins is a rapid, specific and cost efficient methodology. The positive staining is not just highly correlative to the sequencing result, but also correlative to tumor response to TKIs.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 253, Tuesday Morning