Prognostic Significance of TRAIL Signaling Molecules in Stage II and III Colorectal Cancer

Purpose: We previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability and chemotherapy-induced apoptosis in colorectal cancer. In this study, we determined the prognostic significance of c-FLIP, caspase 8, TRAIL and DR5 expression in tissues from patients with stage II and III colorectal cancer.

Experimental Design: Tissue microarrays were constructed from matched normal and tumor tissue derived from patients (n = 253) enrolled in a phase III trial of adjuvant 5-fluorouracil–based chemotherapy versus postoperative observation alone. TRAIL, DR5, caspase 8, and c-FLIP expression levels were determined by immunohistochemistry.

Results: Colorectal tumors displayed significantly higher expression levels of c-FLIP (P < 0.001), caspase 8 (P = 0.01), and DR5 (P < 0.001), but lower levels of TRAIL (P < 0.001) compared with matched normal tissue. In univariate analysis, higher TRAIL expression in the tumor was associated with worse overall survival (P = 0.026), with a trend to decreased relapse-free survival (RFS; P = 0.06), and higher tumor c-FLIP expression was associated with a significantly decreased RFS (P = 0.015). Using multivariate predictive modeling for RFS in all patients and including all biomarkers, age, treatment, and stage, we found that the model was significant when the mean tumor c-FLIP expression score and disease stage were included (P < 0.001). As regards overall survival, the overall model was predictive when both TRAIL expression and disease stage were included (P < 0.001).

Conclusions: High c-FLIP and TRAIL expression may be independent adverse prognostic markers in stage II and III colorectal cancer and might identify patients most at risk of relapse.

'A new sword on an old anvil': W.B.Yeats, Robert Graves and the Anglo-Irish Tradition

Throughout his writing life, Robert Graves was consistently and often publicly hostile to the work of W.B. Yeats, whilst still also owing a considerable debt to the older poet (who he never met). This essay explores Graves' complex responses to Yeats, arguing that his antagonism may be understood in the light of his own Anglo-Irish background, and is implicated in his relations with his father, Alfred Perceval Graves, as well as his experience of the First World War. Probing the suggestiveness of Graves's claim in 1959 that his poems 'remain true to the Anglo-Irish poetic tradition into which I was born', it traces the relation between Yeats and Graves through correspondence, critical writings, and through a comparative reading of Yeats's A Vision and Graves's The White Goddess, and reveals underlying similarities in their critical and mythological thinking in spite of Graves's public disavowal of the Yeatsian aesthetic.