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J. Li
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-027 - Responses to Crizotinib in Six Lung Adenocarcinoma Patients of ALK IHC-Positive and FISH-Negative (ID 2152)
09:30 - 09:30 | Author(s): J. Li
- Abstract
Background:
The anaplastic large cell kinase gene (ALK)-positive is a special type of non-small cell lung carcinomas (NSCLC). Although Ventana IHC (D5F3) and FISH showed high coincidence for detecting ALK rearrangement, discordant results exist in some cases. Treatment strategy as well as efficacy of crizotinib in these cases is such an issue. We studied and reported the efficacy of crizotinib in six lung adenocarcinomas patients with ALK IHC positive and FISH negative.
Methods:
All histologic and cytologic specimens were stained by IHC with an anti-ALK monoclonal antibody (D5F3, Roche) with the OptiView DAB IHC Detection Kit (Roche) and OptiView Amplification kit (Ventana Medical Systems, Inc., Tucson, AZ). All histologic and cytologic samples were also tested by FISH, which was carried out using the Vysis ALK Break Apart FISH probe kit. Three samples [one histologic (patient 1) and two cytologic samples (patients 2 and 6), patients’ numbers were listed in Table 1] were still enough to further perform for EML4-ALK fusion by qRT-PCR. Two samples [one histologic(patient 1) and one cytologic sample(patient 6)] were still enough to further perform for next generation sequencing (NGS) analysis (using modified circulating single molecule amplification and resequencing technology, cSMART). The follow up data from 6 lung adenocarcinoma patients with ALK IHC-positive and FISH-negative who received crizotinib treatment were collected.
Results:
Table 1 showed the clinicopathological characteristics and the therapeutic efficacy of crozitinib for 6 patients in the study. The patients have achieved a response rate of 66.7% (4/6). Pathologically, for patient 1, the 3 unique DNA templates with EML4->EXOC6B->ALK fusion were identified in 710 DNA copies in tumor tissue. The fusion ratio is only 0.42%. For patient 6, we detected 75 unique DNA templates in total 495 DNA copies with 15.15% fusion ration in cytologic specimen. The fusion types of patient 1 and 6 were confirmed by sanger sequencing. Some unknown mechanisms caused the 3 gene fragments fusion of patient 1, the complex fusion type and low fusion ratio cause FISH negative.Table 1：Patient Characteristics, pathologic characteristics and molecular tests in 6 cases
ALK FISH: % of split signals by FISH; NGS: Next generation sequencing; +: No progressive disease was observed at the time of analyse.Patient NO. Gender Age Smoking history ALK IHC ALK FISH NGS-ALK PFS (month) Assessment P1 Female 31 Never smoked + 6% E13:EXOC6B :A20 7.46+ Partial response P2 Male 48 Ever smoker + 10% - 11.96+ Stable disease P3 Female 49 Never smoked + 6% - 19.94+ Partial response P4 Male 59 Ever smoker + 6% - 6.60+ Partial response P5 Male 69 Ever smoker + 10% - 15.08+ Partial response P6 Female 65 Never smoked + 12% E13:A2 3.58 Stable disease
Conclusion:
Lung adenocarcinoma patients with ALK IHC-positive and FISH-negative may also response to crizotinib. Ventana IHC is another candidate method for detecting ALK. One new fusion type EML4->EXOC6B->ALK fusion was verified and the patient with this fusion type showed partial response to crozitinib.
