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Raf kinase inhibitor protein expression combined with peritoneal involvement and lymphovascular invasion predicts prognosis in D ukes' B colorectal cancer patients
Author(s) -
Doyle Brendan,
Hagan Suzanne,
AlMulla Fahd,
Scott Lucy,
Harden Sharon,
Paul Jim,
Mulcahy Hugh,
Murray Graeme I,
Sheahan Kieran,
O'Sullivan Jacintha,
Kolch Walter
Publication year - 2013
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12014
Subject(s) - lymphovascular invasion , colorectal cancer , medicine , tissue microarray , oncology , adjuvant therapy , cancer research , cohort , methylation , adjuvant , cancer , pyrosequencing , dna methylation , biology , metastasis , gene expression , gene , genetics
Aims There is controversy regarding the use of adjuvant therapy in patients with Dukes' B colorectal cancer ( CRC ). New markers, identifying high‐risk D ukes' B patients, are needed. Here, we examine the utility of Raf kinase inhibitor protein ( RKIP ) as such a marker and promoter methylation as a mechanism of RKIP down‐regulation. Methods and results We used a tissue microarray of 220 patients with D ukes' B CRC to examine the effect of RKIP expression on survival. Pyrosequencing was used to assess RKIP promoter methylation status. RKIP expression correlated inversely with disease‐specific survival in this cohort. In multivariate analysis, RKIP was found to be an independent prognostic indicator, along with peritoneal invasion and lymphovascular invasion ( LVI ). RKIP promoter hypermethylation was seen in only one of 29 tumours analysed by pyrosequencing. Conclusions Raf kinase inhibitor protein, peritoneal invasion and LVI provide independent prognostic information in this cohort of Dukes' B CRC patients. This demonstrates the potential utility of RKIP in identifying ‘high‐risk’ D ukes' B patients. It is this high‐risk group which is most likely to benefit from close postoperative monitoring and may derive the most benefit from adjuvant therapy.