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Anant Mohan
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-03 - Challenges in PD-L1 Immunoexpression in Liquid Based Cytology Samples of Advanced Stage Non-Small Cell Lung Carcinomas (ID 11311)
16:45 - 18:00 | Author(s): Anant Mohan
- Abstract
Background
Study of programmed death-ligand 1 (PD-L1) expression is essential in patients of advanced lung cancer to determine their eligibility and predict responsiveness for immune-checkpoint inhibitors. Lung cancer is frequently diagnosed on cytology specimens. Although PD-L1 IHC assays are validated on formalin fixed paraffin embedded (FFPE) tissue, evidences are present in literature which showed high concordance of cytology samples with paired biopsies. However liquid based cytology (LBC) processed specimens have not been tested for PD-L1 expression.
a9ded1e5ce5d75814730bb4caaf49419 Method
Immunohistochemistry using the anti-PD-L1 clone SP263 was performed on BD SurePath LBC processed bronchial washing and brushing smears and paired FFPE endobronchial biopsy specimens. The presence of 100 viable tumor cells was considered adequate for PD-L1 testing. Staining was interpreted positive if membranous and/or cytoplasmic protein expression at any intensity greater than background staining was detected in at least 25% of tumor cells.
4c3880bb027f159e801041b1021e88e8 Result
There were 26 patients with 13 adenocarcinomas and 13 squamous cell carcinomas which were diagnosed by bronchial brushings, washings and concurrently obtained endobronchial biopsy. Twelve out of total 26 biopsies showed cytoplasmic and membranous PD-L1 positivity in >25% tumor cells (46%). Corresponding LBC smear showed PD-L1 positivity in 9 cases establishing concordance of 88.4%. No negative case was positive on cytology. However, there were following challenges while interpreting PDL1 IHC on LBC processed smears: 1. Thick clusters of cells: LBC can cause rounding up of epithelial cells and create thick clusters of tumor cells. Therefore, it was necessary to see under higher magnification (40x) for proper interpretation of membrane staining. 2. Identification of tumor cells: Although identification of tumor cells was done before PD-L1 staining, after staining they were interpreted only on higher magnification to better differentiate them from alveolar macrophages. 3. PD-L1 staining in macrophages: Five cases showed very strong cytoplasmic positivity in macrophages. Since tumor cells showed cytoplasmic and membranous positivity it was easy to differentiate tumor cell positivity from macrophage positivity. Necrotic background in one case stained strongly with PD-L1 immunocytochemistry. 4. Nuclear positivity of PD-L1 positivity: One case, where corresponding biopsy was positive for PD-L1 IHC, showed aberrant nuclear positivity.
8eea62084ca7e541d918e823422bd82e Conclusion
PD-L1 IHC can be performed on LBC processed smears. Though there are challenges in interpretation of immunoexpression inherent to the LBC smears, they can be used in situations when histology material is not available. Future studies are needed to determine their ability to predict response to immunotherapy.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.11 - Screening and Early Detection (Not CME Accredited Session) (ID 960)
- 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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P2.11-17 - MicroRNAs in Exhaled Breath Condensate and Bronchial Brushings as Biomarkers for Early Diagnosis of Lung Cancer (ID 13124)
16:45 - 18:00 | Author(s): Anant Mohan
- Abstract
Background
Lung cancer is one of the primary causes of death worldwide. According to Global Burden of Disease (GBD), highest prevalence and mortality of NSCLC is found in men in India. These typically may present as nodules or masses in the lung. The circulating microRNAs delineate stable and reproducible markers for lung cancer and may play important role in non-invasive diagnostic marker. We have previously discovered miRNA signatures in the exhaled breath condensate (EBC) that are suitable for early diagnostics of various lung diseases. Since miRNAs have roles in the pathogenesis of lung diseases, they can be potentially useful in the early diagnosis of lung cancer and may as well complement the other conventional investigative methods such as low dose computerized tomography (LDCT) to avoid high false positive rates.
Due to paucity of thoracic surgeons and interventional bronchoscopists in India, the inaccessibility of the suspected tumor tissue for pathological diagnosis is a big challenge. All India Institute of Medical Sciences, New Delhi is one of the pioneer institutions that provides medical care to patients coming from different ethnic and socioeconomic backgrounds in India. Based on our previous work and expertise in this area along with emerging consensus in the field, this work is expected to yield promising outcomes.
a9ded1e5ce5d75814730bb4caaf49419 Method
Exhaled Breath Condensate Collection:
Samples were collected from the suspected NSCLC patients during OPD by using RTube.
miRNA isolation from
c-DNA synthesis using Quantimir qPCR kit
qPCR reaction setup for profiling
Bronchoscopy procedure:
Bronchial brushings were collected after obtaining written informed consent during routine diagnosis.
miRNA isolation
c-DNA synthesis by using Kit from Applied Biosystems
qPCR reaction setup by using Kapafast SybrGreen
4c3880bb027f159e801041b1021e88e8 Result
In this study, we found the pro tumorigenic miRNAs like miR-19a, miR-33b, miR-558 are found to be upregulated and anti-tumor miRNAs like let7b, miR-132 and miR-181c found to be downregulated in the exhaled breath of NSCLC patients. Further we validated these miRNAs in bronchial brushings samples taken from respected patients. Surprisingly; those miRNAs showed positive trend.
8eea62084ca7e541d918e823422bd82e Conclusion
In this study, we have found various differentially expressed MicroRNAs in the exhaled breath as well as bronchial brushings samples taken from diagnosed NSCLC patients. The known pro tumorigenic miRNAs were found to be upregulated and anti tumorigenic miRNAs were downregulated. Hence, these biomarkers could either be used as a preliminary non-invasive screening method for the diagnosis of NSCLC. Apart from this, these identified miRNAs could be novel therapeutic targets for the treatment of NSCLC.
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