Tumor heterogeneity determined with a γH2AX foci assay: A study in human head and neck squamous cell carcinoma (hHNSCC) models

• Published in: Radiotherapy and oncology 2017-09, Vol.124 (3), p.379-385
• Main Authors: Rassamegevanon, Treewut, Löck, Steffen, Range, Ursula, Krause, Mechthild, Baumann, Michael, von Neubeck, Cläre
• Format: Article
• Language: English
• Subjects: Animals; Biomarker; Biopsy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - radiotherapy; Cell Line, Tumor; Female; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - radiotherapy; Histones - metabolism; Humans; Immunohistochemistry; Male; Mice; Mice, Nude; Models, Biological; Oxygen - metabolism; Radiation Tolerance; Radiosensitivity; Squamous Cell Carcinoma of Head and Neck; Tumor heterogeneity; Xenograft Model Antitumor Assays; γH2AX foci
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2017.06.027

This study aimed to analyze the intra-tumoral heterogeneity of γH2AX foci in tumor specimens following ex vivo radiation to evaluate the potential of γH2AX foci as predictors for radiosensitivity. γH2AX foci were quantified in tumor specimens of 3hHNSCC tumor models with known differences in radiosensitivity after reoxygenation in culture medium (10h, 24h), single dose exposure (0Gy, 4Gy), and fixation 24h post-irradiation. Multiple, equally treated samples of the same tumor were analyzed for foci, normalized and fitted in a linear mixed-effects model. The ex vivo reoxygenation time had no significant effect on γH2AX foci counts. A significant intra model heterogeneity could be shown for FaDu (p=0.033) but not for SKX (p=0.167) and UT-SCC-5 (p=0.082) tumors, respectively. All tumor models showed a significant intra-tumoral heterogeneity between specimens of the same tumor (p