1. Tumour heterogeneity poses a significant challenge to cancer biomarker research.
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Cyll, Karolina, Ersvær, Elin, Vlatkovic, Ljiljana, Pradhan, Manohar, Kildal, Wanja, Avranden Kjær, Marte, Kleppe, Andreas, Hveem, Tarjei S, Carlsen, Birgitte, Gill, Silje, Löffeler, Sven, Haug, Erik Skaaheim, Wæhre, Håkon, Sooriakumaran, Prasanna, Danielsen, Håvard E, Ersvær, Elin, Avranden Kjær, Marte, Löffeler, Sven, Wæhre, Håkon, and Danielsen, Håvard E
- 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. [ABSTRACT FROM AUTHOR]- Published
- 2017
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