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Norma Yanet Hernandez-Pedro
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-041 - CD47 Expression and Prognosis in a Cohort of Patients with Lung Adenocarcinoma (NSCLC) (ID 10301)
09:30 - 09:30 | Author(s): Norma Yanet Hernandez-Pedro
- Abstract
Background:
CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha, inhibiting phagocytosis. Data on the clinical significance of CD47 expression in patients with different NSCLC subtypes remains limited.
Method:
173 treatment-naïve patients with NSCLC diagnosis were evaluated. Tumor samples obtained by biopsy or surgical resection were collected for CD47 evaluation by immunohistochemistry. Tumor samples were scored according to the fraction of stained cells at each intensity. Staining intensity of cell membrane was visually scored on a scale from 0-3, (0 indicating absent staining and 3 representing maximal staining). In order to assess the prognostic and predictive value of CD47 as a biomarker, patients were stratified according to a cutoff point. This cutoff was optimized as a function of overall survival (OS) using the X-tile and Cutoff Finder software. CD47 mRNA was measured by RT-PCR.
Result:
CD47 ≥ 150 was associated with EGFR mutations in 73% of the positive cases (n=35, p=0.002). Longer overall survival was associated with ECOG 0-1 (p=0.006), adenocarcinoma histology (p=0.009) EGFR mutation status (p=0.001) and the H-score for CD47 (p=0.021). Multivariate analysis supports CD47 as an independent factor for survival (HR 1.8 IC95%: 1.1-2.8; p=0.007) Table 1. Patients with high levels of CD47 mRNA expression correlated with the score of CD47 ≥ 150 (p=0.066).
Conclusion:
The immune checkpoint molecule CD47 expressed on the surface of tumor cells allows them to escape immunosurveillance and therefore higher CD47 expression confers worse prognosis. Figure 1
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-075 - Genomic Changes and Clinical Characteristics Associated with Wood-Smoke Exposure in Patients with Non-Small Cell Lung Cancer (ID 10324)
09:00 - 09:00 | Presenting Author(s): Norma Yanet Hernandez-Pedro
- Abstract
Background:
Chronic wood smoke exposure (WSE) is related to obstructive pulmonary disease and represents an increased risk of lung cancer. WSE is asociated with EGFR-mutations and low frequency of KRAS mutations. WSE signaling networks show better response to EGFR-TKIs, improving response rate and overall survival in NSCLC patients. Next-generation sequencing (NGS) has facilitated parallel analysis of multiple genes for treatment selection and monitoring response to treatment. We evaluated genomic alterations in patients with WSE based on tumor profiling by massive parallel sequencing.
Method:
52 patients with advanced lung cancer were evaluated. Fresh-frozen samples were used for DNA extraction with the Wizard Genomic DNA Purification Kit (Promega) including some formalin-fixed paraffin-embedded tissues (FFPE). The TruSeQ Cancer Panel (Illumina) was used for library construction in targeted sequencing of 48 genes spanning 212 amplicons in mutation hotspots.
Result:
WSE was more frequent in women (59% vs 41% p=0.038). We found diferent mutations in ATM (A1309H, G1679V, N1793I and T2749P), EGFR exon 7 (G288V), KDR (H267, Q1146S) and SMARCB1 (T72Q, G157A). WSE correlated with mutations in the genes KDR 89% vs. 11% (p=0.024), ATM 72% vs. 27% (p=0.040), SMARCB1 74% vs. 26% (p=0.020) and in exon 7 of EGFR 75% vs. 25% (p=0.034). Additionally, ATM mutations correlated with metastasis in CNS and bones 77% vs. 23% (p=0.006), also, patients with EGFR exon 7 presented major metastases in CNS and bones 67 vs. 33 % (p=0.084). SMARCB1 mutations were associated with worse overal survival (48 vs 5.6 months p=0.066). WSE patients carrying EGFR exon 7 mutations had better response showing either partial response or stable disease.
Conclusion:
Latin American patients of lung cancer and WSE present a distinctive mutation profile compared to non-WSE patients showing a positive correlation with KDR, ATM, EGFR exon 7, and SMARCB1 mutations. Figure 1
