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A. Fisseler-Eckhoff



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-023 - Anaplastic Lymphoma Kinase (ALK)-detection in Non-small Cell Lung Cancer: results of the first European IHC-based (D5F3-Optiview) panel test within 16 institutes (ID 1825)

      09:30 - 09:30  |  Author(s): A. Fisseler-Eckhoff

      • Abstract

      Background
      The study was supported by Ventana Medical Systems, Inc., a Member of the Roche Group Background: The reliable identification of NSCLC patients with anaplastic lymphoma kinase (ALK) gene rearrangement is crucial for the prescription of ALK tyrosine kinase inhibitors (e.g. crizotinib). Whereas the US FDA-approval (2011) is based upon FISH-testing, the European EMA-approval (2012) refers to the definition of “ALK-positive” NSCLCs without mandating a particular test. Therefore a reliable ALK-immunohistochemistry (IHC) could be a promising option in daily routine practice.

      Methods
      Material and methods: To test the reliability of ALK-IHC-diagnosis in a multi-centre environment (17 European institutes from Belgium, Denmark, France, Germany, Scotland, Spain, Sweden and Switzerland) two tissue microarrays (TMA) consisting of 15 NSCLC cases (all adenocarcinomas; 3 cores for each case) were independently tested for ALK-expression by each laboratory using Ventana Medical System’s ALK (D5F3) primary antibody combined with OptiView DAB IHC detection and OptiView Amplification kits. Cases included in the study were unequivocal ALK-break positive or negative (by FISH), as well as so called “ALK-borderline” cases (low percentage of ALK-break positive cells by FISH, around the cut-off of 15%, therefore challenging in diagnosis, but PCR-confirmed as harbouring EML-4-ALK-fusion variants and thus eligible for therapy). Prior to the TMA-based case testing, each participating instrument was qualified using the VENTANA ALK 2 in 1 Control Slides. To provide a uniform baseline interpretation, a webinar-based training was given to all observers. This training included an overview of the ALK Interpretation Guide, a guided review of 50 patient cases using digital whole slide images, and a proficiency exam certifying each observer.

      Results
      Results: Detailed data analysis was only partly accomplished at the time of abstract submission and will be presented in detail at the “World Conference on LUNG Cancer” in Sydney. Besides the binary evaluation of the cases (ALK-negative vs. ALK-positive) observers were asked to estimate the staining intensity (0-3) within positive cases in correlation to the number of tumor cells and to generate the H-score.

      Conclusion
      Conclusion: Referring to the EMA-approval text our multi-centre study may contribute to validation and accuracy of IHC-based ALK-testing. Such a validated and reliable IHC-assay could be used: (a) as a good pre-screening method reducing time consuming and costly FISH analysis (shorten turn-around time for test results) and (b) as a final predictive approach in cases with reduced interpretability of FISH results (e.g. minimal tumor cell content in small biopsies, decalcified or artificial altered tissue, FISH in doubt/”borderline”).

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    P2.01 - Poster Session 2 - Cancer Biology (ID 145)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.01-025 - Differential miRNA Expression in Neuroendocrine Tumours of the Lung (ID 2211)

      09:30 - 09:30  |  Author(s): A. Fisseler-Eckhoff

      • Abstract

      Background
      Four neuroendocrine subtypes are distinguishable which differ in the extent of differentiation and grade of biological aggressiveness. Therefore the differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. However, for pathologists it is often a challenge to establish a faithful differential diagnosis with an accurate prognosis which is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts. Thus we investigated two types of miRNAs as an additional tool for differential diagnosis and possible molecular targets.

      Methods
      A collective of 38 patients suffering from well to poorly differentiated neuroendocrine lung tumours were examined. Two different miRNAs (miR-21, miR-34a) were investigated in four distinct subtypes of pulmonary neuroendocrine tumours by comparative gene expression analysis.

      Results
      miRNA 21 was upregulated in G3-neuroendocrine tumors (Mean rank: 26.8; 28.75) as compared to carcinoids (mean rank: 12.33; 12.07) with a significance of 0.00033. High-expression level of miRNA 34a was associated with atypical carcinoids (p = 0.010).

      Conclusion
      miRNAs are suitable candidates for differential neuroendocrine lung cancer diagnosis. A close association is implicated between the elevated miR-21 in high-grade and miR-34a in low grade atypical neuroendocrine lung carcinomas which could potentially be exploited as practical supportive markers for differential lung cancer diagnosis in routine. However, some additional research and validation studies are needed to utilize them as routine markers or potential molecular targets for personalized medicine.