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B. Chewaskulyong
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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): B. Chewaskulyong
- 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): B. Chewaskulyong
- 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.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-097 - Expression of GM2 Activator Protein as a Potential Biomarker for Lung Cancer (ID 2206)
09:30 - 09:30 | Author(s): B. Chewaskulyong
- Abstract
Background:
Lung cancer is a leading cause of cancer-related worldwide. Finding effective biomarkers for early diagnosis would be useful for potential curative treatment. GM2activator protein (GM2AP) is a glycoprotein acting as a cofactor for gangliosideGM2 degradation. GM2AP also associated with the changing levels of ganglioside which has role in tumor invasion, progression and metastases. This study aims to investigate and validate the potential of GM2AP as a lung cancer biomarker.
Methods:
The study was done from September 2011 to June 2013. Serum and urine samples were obtained from lung cancers patients and healthy volunteers from Thailand and Taiwan. The expression level of GM2AP was using two-dimensional gel electrophoresi (2-DE), Western blotting and enzyme linked immunosorbine ent assay (ELISA). This studly was approved by the local research ethics committee . Statistical analysis was performed using SPSS version 17.0. Paired samples t-test and one-way analysis of variance (ANOVA) were used to analyze in different groups. A confidential level of 95% (P<0.05) was consider statistically significant.
Results:
Thailand data There were total 48 lung cancer patients (male 33, female 15) and 44 healthy volunteers . The mean age of study cases and controlled group were 53.3 years (range 2-74) and 42.1 years (range 25-74) respectively. The mean of GM2AP level in lung cancer patiens was 1.60+/-1.21 ng/mL, whereas in healthy controls the levels was 0.21+/-0.14 ng/mLThe expression levels of urine and serum GM2AP were significantly increased when compared to those from healthy controls (P<0.05). The urine GM2AP level of lung cancer patients was 7.62+/-1.06 fold on the median. Moreover the urinary GM2AP level in the male patients (1.16+/-1.07 ng/mL) was higher than in female patients (1.13 +/-1.05 ng/mL). According to histologic subtype, the urinary GM2AP level measured in patents with adenocarinoma, small cell carcinoma and sqaumous cell carcinoma were 1.25+/-1.12, 1.48+/-1.35 and 2.27+/-2.20 ng.ml, respectively. From ROC curve of urinary GM2AP showed sensitivity of 90.91% and specificity of 91.67%.The expression levels of GM2AP of all patiens were included in the statistical analysis and significant correlation (P<0.05) was found with histology cancer types, whereas gender and pathological stage were not correlated. Taiwan data There were 133 lung cancer patients (male 60,female 73) with a mean age of 62 (range 30-81 years). The mean urinary GM2AP level in lung cancer patients was 1.46+/-1.55 ng/mL where as in controlled group was 0.18+/-0.19 ng/mL. There was a 8.03 +/- 1.36 fold increase of GM2AP level in urine and a 5.41+/-0.73 ng/mL. increase in the serum compared to the controlled group. From ROC curve provides 88.46% sensivity and 85.71% specificity in urine G2AP. The mean seum GM2AP level was 0.92+/- 0.27 and controlled group was 0.17+/-0.07 ng/mL. The ROC curve from serum G2AP provides 100% sensitivity and 82.71% specificity. No difference was shown in urinary or serum GM2AP levels when stratified by gender, smoking status , EGFR status or histology subtypes except for the pathology stage.
Conclusion:
Our data suggest that the GM2AP may be useflul as a biomarker for early diagnostic and prognostic in lung cancer.
