Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer
- Elizabeth M Tweedle1,2,
- Ilyas Khattak1,
- Chin Wee Ang1,
- Taoufik Nedjadi1,
- Rosalind Jenkins2,
- B Kevin Park2,3,
- Helen Kalirai4,
- Andy Dodson5,
- Bahram Azadeh5,
- Monica Terlizzo6,
- Heike Grabsch7,
- Wolfram Mueller8,
- Sun Myint9,
- Peter Clark2,8,
- Helen Wong6,
- William Greenhalf1,
- John P Neoptolemos1,2,
- Paul S Rooney10,
- Eithne Costello1,2
- 1Division of Surgery and Oncology, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK
- 2Liverpool Experimental Cancer Medicine Centre, University of Liverpool, Liverpool, UK
- 3MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
- 4Cancer Tissue Bank Research Centre, Department of Pathology, University of Liverpool, Liverpool, UK
- 5Department of Pathology, Royal Liverpool University Hospital, Liverpool, Liverpool, UK
- 6Department of Pathology, University Hospitals Aintree, Fazackerley, Liverpool, UK
- 7Section of Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
- 8Gemeinschaftspraxis Pathologie Starnberg, Germany
- 9Centre for Clinical Oncology, Clatterbridge, Wirral, UK
- 10Department of Colorectal Surgery, Royal Liverpool University Hospital, Liverpool, UK
- Correspondence to Eithne Costello, Division of Surgery and Oncology, Royal Liverpool University Hospital, 5th Floor UCD Building, Daulby Street, University of Liverpool, Liverpool, CH48 4DQ, UK;
- Accepted 4 June 2010
Objective There are currently no biomarkers in routine clinical use for determining prognosis in rectal cancer. In a preliminary proteomic study, variation in the levels of heat shock protein 27 (HSP27) in colorectal cancer samples was observed. The expression of HSP27 in a cohort of 404 patients with colorectal cancer with a predominantly poor prognosis was characterised and an investigation was undertaken of whether the differences were related to clinical outcome. HSP27 levels in diagnostic rectal biopsies were compared with matched surgical samples to determine whether changes in expression occurred in the time between biopsy and surgery and to investigate whether preoperative radiotherapy affected expression. Finally, the relationship between HSP27 expression and outcome was examined in an independent cohort of 315 patients with a predominantly good prognosis.
Methods HSP27 levels were determined using combined two-dimensional gel electrophoresis and tandem mass spectrometry (12 cases) and by immunohistochemistry using tissue microarrays of colorectal cancers sampled at surgery and 80 diagnostic rectal biopsies.
Results HSP27 overexpression was strongly associated with poor cancer-specific survival in rectal cancer (n=205, p=0.0063) but not colon cancer (n=199, p=0.7385) in the cohort with a poor prognosis. Multivariate Cox regression confirmed nodal metastases (p=0.0001) and HSP27 expression (p=0.0233) as independent markers of survival in rectal cancer. HSP27 levels remained unchanged in the majority of cases (65/80, 81%) between diagnostic biopsies and matched surgical samples, regardless of whether patients had undergone preoperative radiotherapy. In the cohort with a good prognosis the association between HSP27 and survival was not observed in patients with either rectal (n=115; p=0.308) or colon cancer (n=200; p=0.713).
Conclusion In a large cohort of patients with a poor prognosis, HSP27 is an independent marker of poor outcome in rectal cancer; its expression is not altered by neoadjuvant radiotherapy. This finding requires validation in an independent similar cohort of patients with rectal cancer. HSP27 levels merit evaluation as a stratification factor for treatment of rectal cancer.
- rectal cancer
- colorectal carcinoma
Funding This work was supported by a Royal College of Surgeons of England Fellowship to EMT and by joint CR-UK/NIHR funding grant number ECMC GRANT C6665/A7348.
Competing interests None.
Ethics approval This study was conducted with the approval of the Liverpool LREC.
Provenance and peer review Not commissioned; externally peer reviewed.