Tumour heterogeneity poses a significant challenge to cancer biomarker research
Menée à partir de l'analyse d'échantillons de prostatectomie radicale issus de 304 patients atteints d'un cancer de la prostate (durée médiane de suivi : 10 ans), cette étude met en évidence une hétérogénéité tumorale en termes d'agressivité (Score de Gleason), de ploïdie cellulaire et d'expression de PTEN, et montre ainsi la difficulté d'identifier des biomarqueurs
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.
British Journal of Cancer , article en libre accès, 2016