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J. Buczkowski
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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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P3.02-045 - Prevalence of ALK Gene Abnormalities in Routine Diagnostics of Polish NSCLC Patients (ID 9524)
09:30 - 09:30 | Author(s): J. Buczkowski
- Abstract
Background:
In NSCLC patients, ALK gene rearrangement should be diagnosed using fluorescence in situ hybridisation (FISH) method. However, immunohistochemistry (IHC) is considered as screening method for expression of ALK abnormal protein. There are discrepancies regarding the specificity of both methods and result interpretation.
Method:
1102 Polish NSCLC patients (85,7% of adenocarcinoma, 443 female, 659 male, median age: 65 years) were analysed for EGFR gene mutations using real-time PCR, after that for ALK abnormalities using IHC technique with D5F3 antibody, followed by FISH method using Vysis molecular probe.
Result:
ALK rearrangements detected by FISH method were confirmed in 49 (4.5% of all patients) out of 203 cases (18.4% of all patients) with ALK abnormal protein expression (specificity of IHC test – 85.4%). The median age of patients with EGFR gene mutations was 65 years, with ALK rearrangement 64 years (p=0.1040) and without these changes - 65 years (p=0.4932). ALK rearrangement was significantly more frequently detected in women (28 cases, 6.3%) than in men (21 cases, 3.2%; p=0.0134) and in FFPE tissue (46 case, 5.9%) than in cell-blocks (3 cases, 0.95%; p=0.0003). Median percentage of nuclei with ALK rearrangement in ALK-positive patients was 25%. In ALK-positive cases, ALK rearrangement defined as coexistence of single red and split signals were observed in 27 cases (55.1%), only split signals were observed in 1 case (2%) and only single red signals were diagnosed in 21 patients (42.9%). In this group of patients, median percentage of single red signals per nuclei was 45%, split signals – 8%, and fused signals – 47%. The polysomy (≥4 gene copy number per nuclei) of ALK gene was observed in 43 (36% of all FISH diagnosed patients) cases.
Conclusion:
The IHC method as a screening method is characterized by relatively low specificity. Cell blocks are a rather difficult material for ALK abnormalities analyzes (probably high risk of false negative results). The interpretation of FISH results with predominant single red signals requires considerable attention.
