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E. Rodriguez Zarco
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-047 - Testing EGFR and ALK in Large Cell Neuroendocrine Carcinoma of the Lung. Looking for Biological Features in Rare Tumors (ID 9612)
09:30 - 09:30 | Author(s): E. Rodriguez Zarco
- Abstract
Background:
Large-cell neurodendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma. It is a very rare tumor, approximately 3% of all lung malignancies. Despite LCNEC responds to cisplatin-based chemotherapy prognosis remains poor. We try to Identify positive cases for EGFR mutations and ALK rearrangement by using fluorescence in situ hybridization (FISH) as gold standard and its correlation with immunohistochemistry (IHC) in LCNEC aming to find new therapeutic options for those patients.
Method:
Patients with LCNEC in our Hospital between 1998 and 2017 were included; classification were originally performed according to the WHO2004 scheme and updated to the WHO2015 scheme. EGFR mutation was determined on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue with the cobas® EGFR Mutation Test v2. ALK FISH testing was performed using the Vysis ALK break-apart FISH kit (Abbott Molecular). At least 50 non-overlapping nuclei were scored by two FISH assays expert pathologists. A higher number of nuclei (100) was counted in cases with the results close to cut-off values.Tumours were interpreted as positive if a split pattern and/or single orange signal without a corresponding green signal were identified in at least 15% of tumour cells ALK IHQ test was performed retrospectively on freshly cut 4-lm thick FFPE tissue sections using anti-ALK (D5F3 clone) rabbit monoclonal antibody on a BenchMark XT autostainer with the Ultraview diaminobenzidine (DAB) detection kit. Staining was positive if tumour cells showed moderate or strong multifocal or diffuse expression. Positive cases showed granular cytoplasmic pattern. Cases were considered concordant if ALK FISH and ALK IHC results were identical.
Result:
27 cases, all of them with enough samples for additional EGFR, ALK FISH and ALK IHC testing were identified. Although 4 cases were positive for ALK staining with IHC only one showed expression in more than 90% of tumor cells and it was also positive for ALK rearrangement with FISH. As reported in literature, we have observed some moderate stippling staining in alveolar and peritumoral macrophages with IHC . Only one was EGFR mutated in exon 20, harboring G719X mutation
Conclusion:
To our knowledge very few LCNEC carrying EGFR mutation or ALK rearrangement have been reported. It highlights the possibility of treating those patients with targeted therapy Although we have found good correlation between FISH and IHC, we dare to recommend still as gold standar test, FISH to assess ALK gene rearrangement.
