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01.03.2006 | Original Article

Intratumour T cells, their activation status and survival in gastric carcinomas characterised for microsatellite instability and Epstein–Barr virus infection

verfasst von: Anna Maria Chiaravalli, Maddalena Feltri, Valentina Bertolini, Elena Bagnoli, Daniela Furlan, Roberta Cerutti, Raffaele Novario, Carlo Capella

Erschienen in: Virchows Archiv | Ausgabe 3/2006

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Abstract

Gastric carcinomas (GCs) with high microsatellite instability (MSI) or an Epstein–Barr virus (EBV) infection are prevalently poorly differentiated adenocarcinomas with abundant lymphoid infiltration. The aims of the study were to clarify (1) if tumour-infiltrating lymphocytes (TILs) and cytotoxic-activated TILs are associated with a better clinical outcome in patients with GCs characterised for the presence of MSI and EBV; (2) if the nature and the activation status of TILs are involved in tumour cell apoptosis, evaluated using the M30 antibody, directed against a fragment of cytokeratin-18 caspase-cleaved during early steps of epithelial cell apoptosis. The immunophenotype of TILs and the tumour cell apoptosis were analysed with immunohistochemistry in 96 GCs, including 35 MSI GCs, and 61 GCs without MSI [microsatellite stable (MSS)], 17 of which were EBV+. MSI and MSS/EBV+ GCs displayed a significantly higher mean number of cytotoxic-activated TILs and apoptotic tumour cells than MSS/EBV− GCs (CD8+ TILs/HPF, 21.7 and 69.6 vs 6.4; T-cell intracellular antigen (TIA)-1+ TILs/HPF, 16.7 and 32.05 vs 5.2; granzyme B+ TILs/HPF, 7.5 and 8.6 vs 0.8; perforin+ TILs/HPF, 5.9 and 9.2 vs 0.9; and M30 IR tumour cells, 5.9 and 2.9 vs 2.3%). In addition to the most reliable clinico-pathological parameters (lymph node status, depth of tumour invasion and tumour stage), a univariate analysis showed that the presence of CD3+ TILs higher than 14.9 (p=0.01), CD8+ TILs higher than 9.5 (p<0.05) and MSI (p=0.02) were associated with better overall patient survival. Using a Cox regression model, only a high number of CD3+ TILs (p=0.02) and a low tumour stage (p=0.00001) were identified as independent prognostic factors. In conclusion, our study demonstrates that a high number of CD3+ and CD8+ TILs is a characteristic of MSI- and EBV-associated GCs and represents a favourable prognostic factor, independently of the pathogenesis of GCs.

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Titel: Intratumour T cells, their activation status and survival in gastric carcinomas characterised for microsatellite instability and Epstein–Barr virus infection
verfasst von: Anna Maria Chiaravalli
Maddalena Feltri
Valentina Bertolini
Elena Bagnoli
Daniela Furlan
Roberta Cerutti
Raffaele Novario
Carlo Capella
Publikationsdatum: 01.03.2006
Verlag: Springer-Verlag
Erschienen in: Virchows Archiv / Ausgabe 3/2006
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-005-0066-4

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Intratumour T cells, their activation status and survival in gastric carcinomas characterised for microsatellite instability and Epstein–Barr virus infection

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

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