1196P - Assessment of ALK rearrangement in advanced non-small cell lung cancer using fluorescence in situ hybridization & immunohistochemistry

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Biomarkers
Non-Small-Cell Lung Cancer, Locally Advanced
Presenter Xiaohong Han
Authors X. Han1, L. Ma2, Y. Liu3, N.N. Zhang4, D. Li5, Y. Shi2
  • 1Clinical Labortary, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021 - Beijing/CN
  • 2Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021 - Beijing/CN
  • 3Oncology Dept., Cancer Hospital-China Academy of Medical Sciences, 100021 - Beijing/CN
  • 4Medical Oncology Dept., Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021 - Beijing/CN
  • 5Department Of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021 - Beijing/CN

Abstract

Introduction

Immunohistochemistry assay (IHC) is recommended to screen non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene rearrangement, who are candidates for ALK inhibitor therapy in recent studies. However, which cases should be confirmed by Fluorescent in situ hybridization (FISH) is unclear. We investigated ALK rearrangement using IHC and FISH and evaluated the concordance between IHC and FISH testing.

Methods

One hundred twenty seven paired tumor samples with advanced NSCLC were collected from Cancer Institute/Hospital of Chinese Academy of Medical Sciences. All of these patients who previously received cell cytotoxic regimens therapy had progressive disease. ALK protein was detected by IHC using new clone antibody (D5F3, Cell Signal Techonology, USA). ALK gene rearrangement was evaluated by FISH using Vysis ALK Break Apart FISH Probe kit (Abbott, USA).

Results

One hundred nineteen samples can be evaluated in 127 cases (93.7%). ALK positive samples were 39.5% (47/119) by IHC, and ALK rearrangement samples were 37.8% (45/119) by FISH. The concordance rate is 95% (kappa = 0.894, p < 0.001). All 66 IHC 0 samples were FISH -, 37 of 39 (94.9%) IHC 3 + samples were FISH + , 7 of 8 (87.5%) IHC 2 + samples were FISH + , whereas 1 of 6 (16.7%) IHC 1 + samples were FISH + . Considering FISH as a standard testing, sensitivity and specificity of IHC were 95.6% and 94.6%, respectively, when 2 + and 3 + were regarded as IHC positive and 0 and 1 + as IHC negative. ALK-positive patients were significantly associated with female (p = 0.033), young (p = 0.015) and higher histological grade (p = 0.012) patients.

Conclusion

IHC can be a useful algorithm to evaluate ALK rearrangement in NSCLC screening for ALK targeted therapy. Our findings suggest that ALK with IHC 1 + and 2 + score should be confirmed by FISH testing.

Disclosure

All authors have declared no conflicts of interest.