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Y. Wannasopha
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-017 - The Study of a Relationship between Thyroid Transcription Factor-1 Expression and EGFR Mutations in Unselected Thai Patients with NSCLC (ID 778)
09:30 - 09:30 | Author(s): Y. Wannasopha
- Abstract
Background:
Epidermal growth factor receptor (EGFR) mutation status is a important test to guide treatment with EGFR tyrosine kinase inhibitors (EGFR TKI) effectively. However mutation detection by DNA direct sequencing remains expensive and is not readily available for routine practice in advanced NSCLC in Thailand. Thus a simple alternative method of EGFR mutation detection is required in NSCLC treatment. Recent studies have demonstrated a good association of Thyroid Transcription Factor-1 (TTF-1) with common TKI-sensitive EGFR mutations in NSCLC. We investigated the possibility of the routine test of TTF-1 expression by a simple immunohistochemistry (IHC) method as a potential indicator of common TKI-sensitive EGFR status in unselected Thai patients with non-small cell lung cancer.
Methods:
We collected tissue sample from 91 patients with NSCLC whose EGFR mutation status had previously been detected by DNA direct sequencing from January 2010 to January 2015. TTF-1 was detected by immunohistochemistry method. Results of expression of TTF-1 staining were scored as two categories were negative (no immunostaining or <5% stained cells) and positive (more than 5% positive cells with unequivocal nuclear immunostaining).
Results:
A total of 91 NSCLC samples with available results of molecular-based EGFR mutational status were collected. The common TKI-sensitive EGFR mutation was detected in 38/91 cases (42%) which included Exon19 del in 18/91 cases (20%), Exon 21 (L858R) point mutations in 20/91 cases (22%). The others 4 cases were found with uncommon EGFR mutations included Exon 20 (T790M), Exon18 (G719X), Exon 20 S768I and Exon 20 ins. There was 1 case with EGFR mutations at both Exon18 (G719X) and 20 ins. No mutation detected (wild-type, WT) were found in 48/91 patients. Of all 91 tissue samples were available for TTF-1 IHC testing, 80 of 91 patients were positive for TTF-1 (88%). For 80 patients with adenocarcinoma histology and 10 patients with squamous cell carcinoma history, TTF-1 was positive in 93% and 60 % respectively (P<0.05). The expression of TTF-1 in EGFR 19 del and 21 exon (L858R) mutation groups were significantly higher than the WT group (95% vs 81%, P < 0.05). In only 1 of 38 specimens positive for EGFR mutations was TTF-1 negative. The sensitivity was 97 % and specificity was 17%. Estimated negative predictive values (NPV) of TTF-1 expression for common TKI-sensitive EGFR mutation prevalence rates of 42% was 90%.
Conclusion:
These results indicated that positive TTF-1 expression has a significant positive correlation with common TKI-sensitive EGFR mutation at exon 19 and 21. In high prevalence area of EGFR mutation positive in Thailand, TTF-1 could be a valuable marker of EGFR mutation status.
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P2.04-034 - The Study of EGFR Mutation Specific-Antibody for Detection of EGFR Status in Non-Small Cell Lung Cancer (ID 750)
09:30 - 09:30 | Author(s): Y. Wannasopha
- Abstract
Background:
Specific somatic mutations of the epidermal growth factor receptor (EGFR) associate with increasing response to EGFR tyrosine kinase inhibitors (TKIs) treatment in NSCLC. Assessment of EGFR mutation status by gene-based assay remains expensive and is not routinely reimbursed in Thailand. The objective of this study is to test a simple immunohistochemical (IHC) method using EGFR mutation-specific antibodies for detection of EGFR status.
Methods:
Specimen from 76 NSCLC patients whose EGFR mutation status had been detected by DNA direct sequencing were collected from January 2010 to July 2014 as the reference standard. We performed IHC analyses using 2 EGFR mutation-specific antibodies to E746-A750 del in exon 19 and the other to L858R in axon 21 for all samples. IHC staining were score as 0 (no, or faint staining intensity in <10% tumor cells), 1+ (faint, staining >10%), 2+ (moderate) and 3+ (strong).
Results:
The reference DNA sequencing showed exon 21 L858R EGFR mutations in 17 (22.4%) patients, exon 19 deletions in 12 (15.8%) patients, G719X mutation in 1 (1.3%) patients, exon 20 insertion in 1 (1.3%) patients, multiple sites mutation in 1 (1.3%) patients and no mutation detected in 46 (52.9%) patients. With the DNA sequencing results were set as the reference standard, the prevalence of mutation detected by IHC-based analyses was 25.8% (8/31), 44.4% (8/18), 100% (7/7) and 66.7% (8/12) respectively, for samples with scores 0, 1+, 2+ and 3+. At IHC cut point value 2+, sensitivity and specificity for antibodies L858R were 52.9% wand 98.3 respectively. Likewise for antibodies E746-A750, cut point value 2+ showed sensitivity and specificity as 50.0% and 95.3% E746-A750 respectively. Additional, indicate similar cut point as score 2 ,PPV and NPV were 66.7% and 91.0% for antibodies E746-A750 and 90.0% and 88% for L858R antibodies.
Conclusion:
A simple IHC-based analysis using EGFR mutation-specific antibodies in this study have good correlation with gene-based for EGFR mutation analysis. In Thailand, these simple IHC cost less for five times, have shorter turn around time than gene-based for EGFR mutation analysis and could be useful where molecular-based assay is not readily accessible.
