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E. Urbanska
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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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P3.04-065 - Use of next Generation Sequencing to Distinguish Origin of Poorly Differentiated Carcinomas in the Lung from Carcinomas in Other Organs (ID 2893)
09:30 - 09:30 | Author(s): E. Urbanska
- Abstract
Background:
Next generation sequencing (NGS) is a molecular analysis for concomitantly assessing several genes for mutations and other abnormalities. Thus, NGS can diminish costs and labour time compared to multiple analyses for individual mutations in Non Small Cell Lung Cancer (NSCLC), such as EGFR, ALK or ROS1 mutations. Another important use may be in diagnostic cases, in which it may be difficult to establish whether a tumor is a primary NSCLC, or represents a metastasis from another organ. Molecular[EMU1] events in every compared sample are assessed in order to find a possible gene constellation matching best the primary origin of the disease. This study describes experience with NGS used in this differential diagnostic process
Methods:
The NGS was performed on genomic DNA purified from formalin-fixed paraffin-embedded tumor tissue using the Ion Torrent PGM NGS sequenator and the Ion AmpliSeq Cancer Hotspot Panel version 2 covering the most common hotspot mutations in 50 cancer relevant genes. The sensitivity is 5% tumor cell nuclei and >500 reads for each amplicon was obtained.
Results:
The use of NGS technique as differential diagnostic tool is exemplified in a 77 year male who in 2010 had left renal R0 resection due to papillary urothelial cancer. In January 2015 he subsequently had right lung upper lobectomy for a 22-mm tumor (primary pulmonary adenocarcinoma, CK7- and TTF1-positive, no EGFR- and ALK-mutations) and right lower lobe wedge resection of a 33 mm tumor (undifferentiated carcinoma of uncertain origin, CK7-positive, TTF1-negative). The clinical dilemma was concerning the possible postoperative treatment indication for this patient. Regarding these two lung tumours as an entire disease, it will be T4N0 and thus IIIA stage of NSCLC with strong indication for adjuvant treatment, despite of the age and one-kidney status. However, if these two resected lung tumours represent different cancers, the tumour in the upper lobe will be staged as IB (T2aN0) and possible benefit of adjuvant chemotherapy for this patient will be limited. NGS showed that each of these three tumors had one unique hotspot mutation, i.e. the urological tumor had BRAF mutation (c.1405_1406GG>TC, p.G469S), the right lung upper lobe tumor had KRAS mutation (c.35G>C, p.G12A), and the right lower lobe tumor had HRAS mutation (c.182A>G, p.Q61R). Thus, the theoretic possibility that the right lower lobe tumor was a metastasis from the urological tumor was not supported and the patient accordingly not considered as having metastatic relapse of the urological cancer, but two primary NSCLCs. Thus, the results did not provide a justification to recommend the adjuvant treatment for this patient. A series of NGS uses in the differential diagnostic process will be presented.
Conclusion:
NGS can examine simultaneously several DNA abnormalities such as EGFR mutations, ALK- and ROS1-rearrangements, which all are of interest for treatment possibilities of NSCLC. However, in patients with NSCLC and a carcinoma in another organ, NGS may also be a valuable diagnostic tool for distinguishing poorly differentiated primary NSCLC from metastasis derived from another organ. A series of such cases will be presented.
