Raf Kinase Inhibitor Protein (RKIP), Lympho-Vascular Invasion and Peritoneal Invasion Can Be Used To Identify a High-Risk Group of Stage II Colorectal Cancer Patients
Brendan Doyle, Suzanne Hagan, Fahd Al-Mulla, Lucy Scott, Sharon Harden, Jim Paul, Hugh Mulcahy, Graeme I Murray, Kieran Sheahan, Jacintha O'Sullivan, Walter Kolch. Trinity College, Dublin, Ireland; Glasgow Caledonian University, Glasgow, United Kingdom; Kuwait University, Kuwait, Kuwait; University of Glasgow, Glasgow, United Kingdom; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; St Vincent's University Hospital, Dublin, Ireland; University of Aberdeen, Aberdeen, United Kingdom; University College Dublin, Dublin, Ireland
Background: There is controversy regarding the use of adjuvant therapy in patients with Stage II colorectal cancer (CRC). It is agreed that patients with "high-risk" disease may benefit from adjuvant therapy. However, at present there is little consensus on how to define this group. New markers, identifying high-risk Stage II patients, are therefore needed. Here, we examine the utility of Raf Kinase Inhibitor Protein (RKIP) as such a marker.
Design: We stained a tissue microarray (TMA) of 220 patients with Stage II CRC with an anti-RKIP antibody. The TMA was scored using a semi-quantitative scoring system which assesses both staining intensity and percentage of tissue stained and has been validated in previous studies. The RKIP score was then correlated with survival in both univariate and multivariate analysis.
Results: RKIP expression correlated inversely with disease-specific survival in univariate analysis. In multivariate analysis, RKIP was found to be an independent prognostic indicator, along with lympho-vascular invasion (LVI) and peritoneal invasion (T4 disease). A Prognostic Index (PI) was developed, using these independent prognosticators by assigning a score of 1 to each of the poor prognostic indicators and summing these to give a PI for each tumor. The PI was highly predictive of disease specific survival in this cohort (p<0.01) (Table 1). Moreover, combining those patients with a PI of 2-3 identified a patient group with a 5-year survival of 44% (95%-CI 30-58%), which is similar to that of patients with lymph node positive (Stage III) CRC, a cohort in whom the benefit of adjuvant therapy has been conclusively shown.
Conclusions: RKIP independently predicts disease-specific survival in Dukes-B CRC. Moreover, when incorporated into a PI along with LVI and peritoneal invasion, a high-risk group of Stage II patients can be identified. These may be the patients who would benefit most from adjuvant therapy.
|PI||No of Patients||No Cancer Deaths (%)||5-year survival||Hazard Ratio|