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

Research output: Contribution to journalArticle

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

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Phosphatidylethanolamine Binding Protein
Blood Vessels
Colorectal Neoplasms
Methylation
Survival
Protein Kinase Inhibitors
Down-Regulation
Multivariate Analysis

Keywords

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

Cite this

Raf kinase inhibitor protein expression combined with peritoneal involvement and lympho-vascular invasion predicts prognosis in Dukes B colorectal cancer patients. / Doyle, Brendan; Hagan, Suzanne; Al-Mulla, Fahd; Scott, Lucy; Harden, Sharon; Paul, Jim; Mulcahy, Hugh; Murray, Graeme Ian; Sheahan, Kieran; O'Sullivan, Jacintha; Kolch, Walter.

In: Histopathology, Vol. 62, No. 3, 02.2013, p. 505-510.

Research output: Contribution to journalArticle

Doyle, B, Hagan, S, Al-Mulla, F, Scott, L, Harden, S, Paul, J, Mulcahy, H, Murray, GI, 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, vol. 62, no. 3, pp. 505-510. https://doi.org/10.1111/his.12014
Doyle, Brendan ; Hagan, Suzanne ; Al-Mulla, Fahd ; Scott, Lucy ; Harden, Sharon ; Paul, Jim ; Mulcahy, Hugh ; Murray, Graeme Ian ; Sheahan, Kieran ; O'Sullivan, Jacintha ; Kolch, Walter. / Raf kinase inhibitor protein expression combined with peritoneal involvement and lympho-vascular invasion predicts prognosis in Dukes B colorectal cancer patients. In: Histopathology. 2013 ; Vol. 62, No. 3. pp. 505-510.
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abstract = "AimsThere 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 resultsWe 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.ConclusionsRaf 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.",
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T1 - Raf kinase inhibitor protein expression combined with peritoneal involvement and lympho-vascular invasion predicts prognosis in Dukes B colorectal cancer patients.

AU - Doyle, Brendan

AU - Hagan, Suzanne

AU - Al-Mulla, Fahd

AU - Scott, Lucy

AU - Harden, Sharon

AU - Paul, Jim

AU - Mulcahy, Hugh

AU - Murray, Graeme Ian

AU - Sheahan, Kieran

AU - O'Sullivan, Jacintha

AU - Kolch, Walter

PY - 2013/2

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N2 - AimsThere 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 resultsWe 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.ConclusionsRaf 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.

AB - AimsThere 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 resultsWe 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.ConclusionsRaf 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.

KW - colorectal cancer

KW - dukes's B

KW - prognosis

KW - raf kinase inhibitor protein

KW - stage II

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DO - 10.1111/his.12014

M3 - Article

VL - 62

SP - 505

EP - 510

JO - Histopathology

JF - Histopathology

SN - 0309-0167

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ER -