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Br J Cancer. 2017 Jul 25;117(3):367-375. doi: 10.1038/bjc.2017.171. Epub 2017 Jun 15.

Tumour heterogeneity poses a significant challenge to cancer biomarker research.

Author information

1
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo NO-0424, Norway.
2
Centre for Cancer Biomedicine, University of Oslo, Oslo, NO-0424, Norway.
3
Department of Pathology, Oslo University Hospital, Oslo, NO-0424, Norway.
4
Department of Informatics, University of Oslo, Oslo, NO-0316, Norway.
5
Department of Pathology, Vestfold Hospital Trust, NO-3103 Tønsberg, Norway.
6
Department of Urology, Vestfold Hospital Trust, Tønsberg, NO-3103, Norway.
7
Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
8
Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.

Abstract

BACKGROUND:

The high degree of genomic diversity in cancer represents a challenge for identifying objective prognostic markers. We aimed to examine the extent of tumour heterogeneity and its effect on the evaluation of a selected prognostic marker using prostate cancer as a model.

METHODS:

We assessed Gleason Score (GS), DNA ploidy status and phosphatase and tensin homologue (PTEN) expression in radical prostatectomy specimens (RP) from 304 patients followed for a median of 10 years (interquartile range 6-12). GS was assessed for every tumour-containing block and DNA ploidy for a median of four samples for each RP. In a subgroup of 40 patients we assessed DNA ploidy and PTEN status in every tumour-containing block. In 102 patients assigned to active surveillance (AS), GS and DNA ploidy were studied in needle biopsies.

RESULTS:

Extensive heterogeneity was observed for GS (89% of the patients) and DNA ploidy (40% of the patients) in the cohort, and DNA ploidy (60% of the patients) and PTEN expression (75% of the patients) in the subgroup. DNA ploidy was a significant prognostic marker when heterogeneity was taken into consideration. In the AS cohort we found heterogeneity in GS (24%) and in DNA ploidy (25%) specimens.

CONCLUSIONS:

Multi-sample analysis should be performed to support clinical treatment decisions.

PMID:
28618431
PMCID:
PMC5537489
DOI:
10.1038/bjc.2017.171
[Indexed for MEDLINE]
Free PMC Article

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