Benutzer: Gast  Login
Mehr Felder
Einfache Suche
Titel:

Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer.

Dokumenttyp:
Journal Article
Autor(en):
Kohlruss, Meike; Krenauer, Marie; Grosser, Bianca; Pfarr, Nicole; Jesinghaus, Moritz; Slotta-Huspenina, Julia; Novotny, Alexander; Hapfelmeier, Alexander; Schmidt, Thomas; Steiger, Katja; Gaida, Matthias M; Reiche, Magdalena; Bauer, Lukas; Ott, Katja; Weichert, Wilko; Keller, Gisela
Abstract:
BACKGROUND: The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC. METHODS: TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx. EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing. RESULTS: EBV(+) (HR, 0.48; 95% CI, 0.23-1.02), MSI-H (HR, 0.56; 95% CI, 0.35-0.89) and GS (HR, 0.72; 95% CI, 0.45-1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p < 0.05). In biopsies before CTx, CIN-high predicted tumour regression (p = 0.026), but was not prognostically relevant. CONCLUSION: A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.
Zeitschriftentitel:
Br J Cancer
Jahr:
2021
Band / Volume:
125
Heft / Issue:
12
Seitenangaben Beitrag:
1621-1631
Volltext / DOI:
doi:10.1038/s41416-021-01587-4
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/34671125
Print-ISSN:
0007-0920
TUM Einrichtung:
Institut für Allgemeine Pathologie und Pathologische Anatomie; Institut für Medizinische Statistik und Epidemiologie; Klinik und Poliklinik für Chirurgie; Lehrstuhl für Allgemeinmedizin (Prof. Schneider) (keine SAP-Zuordnung!); Lehrstuhl für Experimentelle Tumortherapie (Prof. Saur)
 BibTeX