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Open Access Research article

Can we accurately report PTEN status in advanced colorectal cancer?

Christopher Hocking1, Jennifer E Hardingham123, Vy Broadbridge1, Joe Wrin12, Amanda R Townsend14, Niall Tebbutt56, John Cooper7, Andrew Ruszkiewicz7, Chee Lee68 and Timothy J Price146*

Author Affiliations

1 The Queen Elizabeth Hospital, TQEH Woodville Road, Woodville South, SA 5011, Australia

2 Bazil Hetzel Institute, Woodville Road, Woodville, SA, Australia

3 University of Adelaide School of Medical Sciences, Adelaide, Australia

4 University of Adelaide School of Medicine, Adelaide, Australia

5 Austin Health, Melbourne, Victoria, Australia

6 Australasian Gastrointestinal Trials Group, Sydney, NSW, Australia

7 SA Pathology, Adelaide, Australia

8 Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

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BMC Cancer 2014, 14:128  doi:10.1186/1471-2407-14-128

Published: 25 February 2014

Abstract

Background

Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results.

Methods

We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed.

Results

Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%).

Conclusion

Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer.

Keywords:
PTEN; Colorectal; Immunohistochemistry; Copy number; Mutation