Raf kinase inhibitor protein expression combined with peritoneal involvement and lympho-vascular invasion predicts prognosis in Dukes B colorectal cancer patients.

Brendan Doyle, Suzanne Hagan, Fahd Al-Mulla, Lucy Scott, Sharon Harden, Jim Paul, Hugh Mulcahy, Graeme Ian Murray, Kieran Sheahan, Jacintha O'Sullivan, Walter Kolch

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16 Citations (Scopus)

Abstract

Aims
There is controversy regarding the use of adjuvant therapy in patients with Dukes' B colorectal cancer (CRC). New markers, identifying high-risk Dukes' 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 Dukes' 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’ Dukes' 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.
Original languageEnglish
Pages (from-to)505-510
Number of pages6
JournalHistopathology
Volume62
Issue number3
Early online date22 Jan 2013
DOIs
Publication statusPublished - Feb 2013

Keywords

  • colorectal cancer
  • dukes's B
  • prognosis
  • raf kinase inhibitor protein
  • stage II

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    Doyle, B., Hagan, S., Al-Mulla, F., Scott, L., Harden, S., Paul, J., Mulcahy, H., Murray, G. I., Sheahan, K., O'Sullivan, J., & Kolch, W. (2013). Raf kinase inhibitor protein expression combined with peritoneal involvement and lympho-vascular invasion predicts prognosis in Dukes B colorectal cancer patients. Histopathology, 62(3), 505-510. https://doi.org/10.1111/his.12014