Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas of the lung

Autor: Sabine Merkelbach-Bruse, Reinhard Büttner, Karl-Friedrich Deml, Maren Meiboom, Elke Binot, Sven Hauke, Katja Schmitz, Hans-Ulrich Schildhaus
Rok vydání: 2013
Předmět:
Adult
Male
Pathology
medicine.medical_specialty
Lung Neoplasms
DNA Mutational Analysis
Chromogenic in situ hybridization
Adenocarcinoma of Lung
Cell Cycle Proteins
Adenocarcinoma
Biology
Pathology and Forensic Medicine
Proto-Oncogene Proteins p21(ras)
Predictive Value of Tests
Proto-Oncogene Proteins
hemic and lymphatic diseases
Biomarkers
Tumor
medicine
Humans
Anaplastic Lymphoma Kinase
Genetic Predisposition to Disease
Genetic Testing
In Situ Hybridization
In Situ Hybridization
Fluorescence
Aged
Aged
80 and over
Gene Rearrangement
Lung
Serine Endopeptidases
Receptor Protein-Tyrosine Kinases
Reproducibility of Results
Signal Processing
Computer-Assisted
Middle Aged
respiratory system
Molecular biology
digestive system diseases
respiratory tract diseases
ErbB Receptors
Phenotype
medicine.anatomical_structure
Chromogenic Compounds
Mutation
ras Proteins
Feasibility Studies
Female
Microtubule-Associated Proteins
Zdroj: Modern Pathology. 26:1468-1477
ISSN: 0893-3952
DOI: 10.1038/modpathol.2013.95
Popis: Reliable detection of anaplastic lymphoma kinase (ALK) rearrangements is a prerequisite for personalized treatment of lung cancer patients, as ALK rearrangements represent a predictive biomarker for the therapy with specific tyrosine kinase inhibitors. Currently, fluorescent in situ hybridization (FISH) is considered to be the standard method for assessing formalin-fixed and paraffin-embedded tissue for ALK inversions and translocations. However, FISH requires a specialized equipment, the signals fade rapidly and it is difficult to detect overall morphology and tumor heterogeneity. Chromogenic in situ hybridization (CISH) has been successfully introduced as an alternative test for the detection of several genetic aberrations. This study validates a newly developed ALK CISH assay by comparing FISH and CISH signal patterns in lung cancer samples with and without ALK rearrangements. One hundred adenocarcinomas of the lung were included in this study, among them 17 with known ALK rearrangement. FISH and CISH were carried out and evaluated according to the manufacturers' recommendations. For both assays, tumors were considered positive if ≥15% of tumor cells showed either isolated 3' signals or break-apart patterns or a combination of both. A subset of tumors was exemplarily examined by using a novel EML4 (echinoderm microtubule-associated protein-like 4) CISH probe. Red, green and fusion CISH signals were clearcut and different signal patterns were easily recognized. The percentage of aberrant tumor cells was statistically highly correlated (P0.001) between FISH and CISH. On the basis of 86 samples that were evaluable by ALK CISH, we found a 100% sensitivity and 100% specificity of this assay. Furthermore, EML4 rearrangements could be recognized by CISH. CISH is a highly reliable, sensitive and specific method for the detection of ALK gene rearrangements in pulmonary adenocarcinomas. Our results suggest that CISH might serve as a suitable alternative to FISH, which is the current gold standard.
Databáze: OpenAIRE
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