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Nagla Abdel Karim
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-129 - Potential Impact of KRAS Molecular Profiling of Non-Squamous Non-Small Cell Lung Cancer (NSCLC). (ID 14472)
16:45 - 18:00 | Presenting Author(s): Nagla Abdel Karim
- Abstract
Background
Several studies suggest that patients with KRAS-mutant (KRASmut) NSCLC fail to benefit from platinum-based systemic chemotherapy and are not likely to have targetable mutations. Molecular profiling has the potential to identify other potential targets that might provide novel therapy for KRASmut NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this study, we purified RNA from archived tumors of patients with stage I and II NSCLC wild-type (wt) and mutant (Mut) KRAS and from paired normal tissue from 20 and 17 patients, respectively, and assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of four genes involved in DNA synthesis and repair including thymidylate synthase (TS), BRCA1, ECCR1, RAP80, and the proto-oncogene, SRC. Additionally, we assessed expression of PD-L1 IHC 22C3 by immunohistochemistry using an antibody against PD-L1 IHC 22C3.
4c3880bb027f159e801041b1021e88e8 Result
Our results show that in KRASmut tumors, ERCC1, TS, and SRC expression were increased in comparison to paired normal lung tissue (p ≤ 0.04). Expression of BRCA1 and RAP80 were similar in both KRASmut tumor and the paired-normal tissue. Furthermore, expression of BRCA1, TS and SRC were significantly increased in KRASwt tumor relative to their expression in normal lung (p ≤ 0.044). Expression of ERCC1 and RAP80 were similar in KRASwt tumors and paired normal tissue. Interestingly, SRC expression in KRASmut tumor was decreased in comparison to KRASwt tumor. There was a notable expression of PD-L1 (cut off level of 50%) in the tumor and surrounding stromal cells in 2 out of 20 KRASmut tumors.
8eea62084ca7e541d918e823422bd82e Conclusion
In conclusion, within the limitation of our retrospective study, KRASmut NSCLC would likely be platinum, taxane and pemetrexed resistant, having a low level of PD-L1 expression. KRAS wt BRCA1 positive tumors tend to be sensitive to taxane therapy and possibly platinum-based drugs. Our result suggests the need to develop targeted therapies for KRASmut NSCLC and other therapies specific to the molecular profile of the tumor.
ERCC1 BRCA1 TS SRC PD-L1 (50%) mt.Kras + - + - 10% Wt.Kras - + + + Normal Lung Tissue - - - -
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.12-05 - The Pattern of PD-L1 Expression in Thoracic Neuroendocrine Tumors (ID 14468)
12:00 - 13:30 | Presenting Author(s): Nagla Abdel Karim
- Abstract
Background
Immunotherapy has assumed a pivotal role in the treatment of a number of cancers including lung cancer through up-regulation of tumor-specific cytolytic T cell activity. The level of expression of programmed death-ligand 1 (PD-L1) on tumor cells play an important role in determining the first-line of therapy in non-small cell lung cancer (NSCLC) with immunotherapy.
Large cell neuroendocrine carcinoma (LCNEC) of the lung has an adverse prognosis, with small numbers of patients suitable for surgical resection at diagnosis. While PD-L1 expression is shown to be an overall negative prognostic factor, it is associated with a positive outcome when PD-1/PD-L1 blocking antibodies are used. In this study, we investigated PD-L1 expression in LCNEC using immunohistochemistry.
a9ded1e5ce5d75814730bb4caaf49419 Method
Thirty-six patients with LCNEC diagnosed between 2007 and 2013 at the University of Cincinnati Medical Center were included. PD-L1 IHC 22C3 expression was analyzed by immunohistochemistry on formalin fixed, paraffin embedded (FFPE) tissue samples using anti-PD-L1 antibody PD-L1 expression in the tumor and surrounding stromal cells was quantitated based on staining intensity (0 to 3+) and stained surface area (0-100%). A grade cutoff of PD-L1 of ≤5% was used to decide positive or negative.
4c3880bb027f159e801041b1021e88e8 Result
We found that 11 of 36 patients showed stromal expression of PD-L1, but only 6 out of 36 patients demonstrated PD-L1 expression on the tumor, and 3 patients were positive for PD-L1 expression in both tumor and surrounding stromal cells.
8eea62084ca7e541d918e823422bd82e Conclusion
In conclusion, PD-L1 expression on stromal cells appears to be higher in patients with LCNEC compared to the PD-L1 expression on the tumor cells. Prior studies have shown that patients with small cell lung cancer, another aggressive neuroendocrine tumor exhibited greater levels of PD-L1 expression on stromal cells and tumor-associated macrophages suggesting a possible alternative predictive marker.
6f8b794f3246b0c1e1780bb4d4d5dc53
