Multi-colour FISH in oesophageal adenocarcinoma-predictors of prognosis independent of stage and grade.
BACKGROUND
Oesophageal adenocarcinoma or Barrett's adenocarcinoma (EAC) is increasing in incidence and stratification of prognosis might improve disease management. Multi-colour fluorescence in situ hybridisation (FISH) investigating ERBB2, MYC, CDKN2A and ZNF217 has recently shown promising results for the diagnosis of dysplasia and cancer using cytological samples.


METHODS
To identify markers of prognosis we targeted four selected gene loci using multi-colour FISH applied to a tissue microarray containing 130 EAC samples. Prognostic predictors (P1, P2, P3) based on genomic copy numbers of the four loci were statistically assessed to stratify patients according to overall survival in combination with clinical data.


RESULTS
The best stratification into favourable and unfavourable prognoses was shown by P1, percentage of cells with less than two ZNF217 signals; P2, percentage of cells with fewer ERBB2- than ZNF217 signals; and P3, overall ratio of ERBB2-/ZNF217 signals. Median survival times for P1 were 32 vs 73 months, 28 vs 73 months for P2; and 27 vs 65 months for P3. Regarding each tumour grade P2 subdivided patients into distinct prognostic groups independently within each grade, with different median survival times of at least 35 months.


CONCLUSIONS
Cell signal number of the ERBB2 and ZNF217 loci showed independence from tumour stage and differentiation grade. The prognostic value of multi-colour FISH-assays is applicable to EAC and is superior to single markers.
1] Department of Pathology, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstrasse 8/10, 91054 Erlangen, Germany [2] Comprehensive Cancer Center Erlangen-European Metropolitan Region Nuremberg 91054 Erlangen, Germany.
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Geppert
Department of Pathology, University Hospital Regensburg, 93053 Regensburg, Germany.
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Rümmele
Department of Pathology and Cytology, 80992 Munich, Germany.
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Sarbia
Department of Pathology, University Bern, CH 3010 Bern, Switzerland.
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Langer
Department of Surgery, Klinikum Rechts der Isar, Technical University Munich, 81675 Munich, Germany.
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Feith
Ventana Medical Systems, Inc., Oro Valley, AZ 85755, USA.
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Morrison
Abbott Molecular, Des Plaines, IL 60018, USA.
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Pestova
1] Department of Pathology, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstrasse 8/10, 91054 Erlangen, Germany [2] Comprehensive Cancer Center Erlangen-European Metropolitan Region Nuremberg 91054 Erlangen, Germany.
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Schneider-Stock
1] Department of Pathology, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstrasse 8/10, 91054 Erlangen, Germany [2] Comprehensive Cancer Center Erlangen-European Metropolitan Region Nuremberg 91054 Erlangen, Germany.
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A
Hartmann
1] Department of Pathology, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstrasse 8/10, 91054 Erlangen, Germany [2] Comprehensive Cancer Center Erlangen-European Metropolitan Region Nuremberg 91054 Erlangen, Germany.
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Rau
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; C489427:MYC protein, human; C113698:ZNF217 protein, human; C508053:ERBB2 protein, human