566P - Prognostic significance of tumour-associated immune response gene expression, ESR1 and clinicopathologic parameters in stage II/III colorectal canc...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Cancer Immunology and Immunotherapy
Rectal Cancer
Translational Research
Presenter George Pentheroudakis
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors G. Pentheroudakis1, V. Kotoula1, G. Raptou1, V. Karavasilis1, G. Gourioti1, C. Papandreou2, K.N. Syrigos3, E. Bournakis4, G. Rallis5, I. Varthalitis6, E. Galani7, G. Lazaridis8, G. Papaxoinis1, D.G. Pectasides9, G. Aravantinos10, K.T. Kalogeras11, T. Makatsoris12, R. Wirtz13, G. Fountzilas14
  • 1Hecog, Hellenic Cooperative Oncology Group, 11524 - Athens/GR
  • 2Department Of Medical Oncology, University Hospital of Larissa, 41110 - Larissa/GR
  • 3Oncology Unit, 3rd Department Of Medicine, Athens University School of Medicine3rd Department of Medicine, GR-115 27 - Athens/GR
  • 4Hematology/oncology Unit, Alexandra Hospital, 115 28 - Athens/GR
  • 5Medical Oncology Clinic, Papageorgiou HospitalAristotle University of Thessaloniki, GR-564 29 - Thessaloniki/GR
  • 6Department Of Medical Oncology, Chania General Hospital ”St. George”, 00000 - Chania/GR
  • 7Medical Oncology, Metropolitan Hospital, GR-185 47 - Athens/GR
  • 8Oncology Ward, Papageorgiou Hospital Aristotle University of Thessaloniki, 564 29 - Thessaloniki/GR
  • 92nd. Dep. Int. Medicine, Hippokration General Hospital, 115 27 - Athens/GR
  • 10Oncology, Agii Anargiri Cancer Hospital, GR-145 64 - Athens/GR
  • 11Data Office, Hellenic Cooperative Oncology Group, Athens/GR
  • 12Dept. Of Internal Medicine, University Hospital Patras, GR-26 500 - Patras/GR
  • 13Stratifyer Molecular Pathology Gmbh (stratifyer, STRATIFYER Molecular Pathology GmbH (STRATIFYER, 50935 - Cologne/DE
  • 14Medical Oncology Clinic, Papageorgiou Hospital Aristotle University of Thessaloniki, 564 29 - Thessaloniki/GR

Abstract

Aim

Tumour-associated immune response and colon cancer site emerge as parameters impacting on disease biology and patient outcome.

Methods

mRNA gene expression of immune response (IR) genes (CD3Z, CD8, CXCL9, CXCL13, IGHM, FOXP3), SNAI2 and ESR1 were quantified by RTqPCR in formalin-fixed tumours of 408 oxaliplatin-treated patients with stage II/III colorectal cancer (trial ACTRN12610000509066). Results were submitted to hierarchical clustering and analysed.

Results

We selected a mRNA gene signature (mRNA 2-cluster immunoscore, mIS2) based on CD3Z and CD8 expression (Cluster 2: upregulated CD3Z CD8 expression; Cluster 1: more heterogeneous but overall downregulated CD3Z CD8 expression). Partitioning analysis including age, stage, site, mIS2 and KRAS gene mutation, revealed that tumour stage, tumour site and mIS2 identified eight patient populations with distinct DFS (p < 0.0001) and OS (p < 0.0001). In stage III CRC, upregulated mIS2 was a favourable prognosticator in Right Colon but had no significance in the Left Colon. In stage II CRC, upregulated mIS2 was non-significantly favourable in Right Colon and downregulated mIS2 was significantly favourable in the Left Colon. Mismatch repair protein and KRAS/BRAF mutation, SNAI2 mRNA, and % of tumour-infiltrating lymphocytes were not prognostic . In multivariate analysis, the Stage_Site_mIS2 partitioning parameter, tumour ESR1 gene expression and necrosis at histology retained independent prognostic significance for malignant relapse and death.

MULTIVARIATE ANALYSIS HR for relapse P-value HR for death P-value
STAGE_SITE_mIS2 0.0008 0.0008
Stage II Right mIS2-downreg 0.23 0.1702 0.17 0.09
Stage II Right mIS2-upreg 0.19 0.1188 0.00 0.98
Stage II Left mIS2-downreg 0.26 0.0466 0.22 0.02
Stage II Left mIS2-upreg 0.62 0.4803 0.46 0.25
Stage III Right mIS2-downreg 3.00 0.0152 2.62 0.02
Stage III Right mIS2-upreg 0.79 0.7355 1.50 0.43
Stage III Left mIS2-downreg 1.43 0.4001 1.04 0.91
Stage III Left mIS2-upreg 1 1
HIGH TUMOUR MRNA EXPRESSION OF ESR1 2.91 0.0003 1.95 0.02
PRESENCE OF NECROSIS 0.42 0.0068 0.39 0.002

Conclusions

The prognostic significance of tumour mRNA-based CD3 and CD8 immune response signature may be distinct in different stages and different sites of colon cancer.

Disclosure

R. Wirtz: Stocks at Stratifyer Molecular Pathology, Cologne, Germany. All other authors have declared no conflicts of interest.