Universität zu Köln

Schildhaus, Hans-Ulrich, Deml, Karl-Friedrich, Schmitz, Katja, Meiboom, Maren, Binot, Elke, Hauke, Sven, Merkelbach-Bruse, Sabine and Buettner, Reinhard (2013). Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas of the lung. Mod. Pathol., 26 (11). S. 1468 - 1478. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0285

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Abstract

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 (P<0.001) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schildhaus, Hans-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Deml, Karl-Friedrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Meiboom, Maren UNSPECIFIED UNSPECIFIED UNSPECIFIED Binot, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauke, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-472874
DOI:	10.1038/modpathol.2013.95
Journal or Publication Title:	Mod. Pathol.
Volume:	26
Number:	11
Page Range:	S. 1468 - 1478
Date:	2013
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1530-0285
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; GROWTH-FACTOR; CANCER; IMMUNOHISTOCHEMISTRY; IDENTIFICATION; AMPLIFICATION; RELIABILITY; CARCINOMAS; INHIBITOR Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47287