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Overexpression of protein S100A4 is independently associated with overall survival in stage C colonic cancer but only in cytoplasm at the advancing tumour front
Authors:P. S. S. Kho  L. Jankova  C. L.-S. Fung  C. Chan  C. Clarke  B. P. C. Lin  G. Robertson  M. Molloy  P. H. Chapuis  E. L. Bokey  O. F. Dent  S. Clarke
Affiliation:1. Department of Medicine, Concord Hospital, Sydney, New South Wales, Australia
2. Cancer Pharmacology Unit, ANZAC Research Institute, Concord Hospital, Sydney, New South Wales, Australia
3. Department of Anatomical Pathology, Concord Hospital, Sydney, New South Wales, Australia
4. Department of Anatomical Pathology, Concord Hospital and Discipline of Pathology, The University of Sydney, Sydney, New South Wales, Australia
5. Australian Proteome Analysis Facility and Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, Australia
6. Department of Colorectal Surgery, Concord Hospital and Discipline of Surgery, The University of Sydney, Sydney, New South Wales 2139, Australia
7. Department of Medicine, Concord Hospital and Discipline of Medicine, The University of Sydney, Sydney, New South Wales, Australia
Abstract:

Purpose

S100A4, a multifunctional protein, has been linked to the invasive growth and metastases of several human cancers. This study investigated the association between S100A4 and overall survival and other clinicopathological features in patients with stage C colonic cancer.

Methods

Clinical and pathological data were obtained from a prospective hospital registry of 409 patients who had a resection for stage C colonic cancer. Tissue microarrays for immunohistochemistry were constructed from archived tissue. S100A4 staining intensity and percentage of stained cells were assessed in nuclei and cytoplasm for both the central part of the tumour and at the advancing front. Overall survival was analysed by the Kaplan–Meier method and Cox regression.

Results

Only a high percentage of cells with S100A4 cytoplasmic staining in frontal tissue was associated with poor survival (hazard ratio, 1.6; 95?% CI 1.1–2.2; p?=?0.008) after adjustment for other prognostic variables. There was no association between frontal cytoplasmic S100A4 expression and any of 13 other clinicopathological variables.

Conclusions

High expression of S100A4 in cytoplasm at the advancing front of stage C colonic tumours indicates a poor prognosis. Whether S100A4 can predict response to adjuvant chemotherapy remains to be investigated in a randomised clinical trial.
Keywords:
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