Tumour heterogeneity poses a significant challenge to cancer biomarker research

• Published in: British journal of cancer Vol. 117; no. 3; pp. 367 - 375
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-07-2017; Nature Publishing Group
• Subjects: 631/67/1244; 631/67/1857; 631/67/2329; 631/67/589/466; Aged; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; Biopsy, Needle; Cancer; Cancer Research; Cancer surgery; Deoxyribonucleic acid; DNA; DNA, Neoplasm - analysis; Drug Resistance; Epidemiology; Genetic Heterogeneity; Heterogeneity; Homology; Humans; Male; Medicin och hälsovetenskap; Middle Aged; Molecular Diagnostics; Molecular Medicine; Neoplasm Grading; Neoplasm Recurrence, Local - genetics; Oncology; Ploidies; Ploidy; Prostate - pathology; Prostate cancer; Prostatectomy; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; PTEN Phosphohydrolase - analysis; PTEN protein; Tensin; Tumor Burden; Tumors; Watchful Waiting; DNA ploidy; Gleason score; PTEN; prostate cancer; heterogeneity; active surveillance
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2017.171

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.