Tumor heterogeneity determined with a γH2AX foci assay: A study in human head and neck squamous cell carcinoma (hHNSCC) models. Issue 3 (September 2017)

• Record Type: Journal Article
• Authors: Rassamegevanon, Treewut; Löck, Steffen; Range, Ursula; Krause, Mechthild; Baumann, Michael; von Neubeck, Cläre
• Is Part Of: Radiotherapy and oncology. Volume 124:Issue 3(2017:Sep.)
• Page Start: 379
• Page End: 385
• Publication Date: 2017-09
• Subjects: γH2AX foci -- Tumor heterogeneity -- Biomarker -- Radiosensitivity; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2017.06.027
• Languages: English
• ISSNs: 0167-8140

Abstract

Abstract: Purpose: 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. Material and methods: γH2AX foci were quantified in tumor specimens of 3 hHNSCC tumor models with known differences in radiosensitivity after reoxygenation in culture medium (10 h, 24 h), single dose exposure (0 Gy, 4 Gy), and fixation 24 h post-irradiation. Multiple, equally treated samples of the same tumor were analyzed for foci, normalized and fitted in a linear mixed-effects model. Results: 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 < 0.01) or among microscopic fields of a particular tumor specimen ( p < 0.0001). Conclusion: Similar results for ex vivo γH2AX foci between 10 h and 24 h reoxygenation time support the applicability of the assay in a clinical setting. The high intra-tumoral heterogeneity underlines the necessity of multiple analyzable samples per patient and therewith the need for an automated foci analysis.