Eleftheria Alexopoulou1, Theodora Katsila1,2, Maria Tolia3, Nikolaos Tsoukalas4, Michael Leontsinidis5, George Kyrgias6, Vasilios Kouloulias7, George P Patrinos2, Despoina Spyropoulou1, Dimitrios Kardamakis8. 1. Department of Radiation Oncology, University of Patras Medical School, Patras, Greece. 2. Department of Pharmacy, University of Patras, Patras, Greece. 3. Department of Radiotherapy, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larisa, Greece. 4. Department of Oncology, Veterans Hospital (NIMTS), Athens, Greece. 5. Department of Public Health, University of Patras Medical School, Patras, Greece. 6. Department of Radiotherapy, Larisa University Hospital, Larisa, Greece. 7. Radiotherapy Unit, ATTIKON University Hospital, University of Athens Medical School, Athens, Greece. 8. Department of Radiation Oncology, University of Patras Medical School, Patras, Greece kardim@upatras.gr.
Abstract
BACKGROUND/AIM: Radiation dermatitis is observed in 95% of breast cancer patients receiving radiotherapy. The aim of this study was to explore the correlation between protein expression in tumor cells and the risk of developing radiation dermatitis. PATIENTS AND METHODS: Breast cancer patients receiving postoperative radiotherapy were included in this study. Tumor specimens from 122 patients were examined by immunohistochemistry for the expression of Ki67, ataxia telangiectasia mutated (ATM) kinase, hypoxia-inducible factor-1-alpha (HIF-1a), inducible nitric oxide synthase (iNOS), and a-glucosidase (aGluc). The findings were correlated with the occurrence and severity of radiation dermatitis (Radiation therapy oncology group-RTOG grading scale), taking into consideration body weight and skin type (Fitzpatrick system). Data were explored further via pathway and network analyses. RESULTS: Correlation of radiation dermatitis (RTOG scale) with the observed increased expression of Ki67, ATM, iNOS, HIF-1a and aGluc, failed to reach statistical significance when skin type and/or body weight were considered. Network interactions of proteins involved in tumor growth (Ki67, ATM) and/or affect the oxidation state of the cell (HIF-1a, iNOS, aGluc) were revealed, that may contribute to the risk of developing acute radiation dermatitis. CONCLUSION: Correlation of the increased expression of the studied proteins and the occurrence and severity of radiation dermatitis in women undergoing postoperative radiotherapy, failed to reach statistical significance. Pathway and network analyses predicted that vasodilation and angiogenesis may contribute to radiation-induced dermatitis via mechanisms that need to be further explored. Our strategy serves as a paradigm for coupling histopathological data to molecular findings and network analyses for risk assessment in the clinic. Copyright
BACKGROUND/AIM: Radiation dermatitis is observed in 95% of breast cancerpatients receiving radiotherapy. The aim of this study was to explore the correlation between protein expression in tumor cells and the risk of developing radiation dermatitis. PATIENTS AND METHODS: Breast cancerpatients receiving postoperative radiotherapy were included in this study. Tumor specimens from 122 patients were examined by immunohistochemistry for the expression of Ki67, ataxia telangiectasia mutated (ATM) kinase, hypoxia-inducible factor-1-alpha (HIF-1a), inducible nitric oxide synthase (iNOS), and a-glucosidase (aGluc). The findings were correlated with the occurrence and severity of radiation dermatitis (Radiation therapy oncology group-RTOG grading scale), taking into consideration body weight and skin type (Fitzpatrick system). Data were explored further via pathway and network analyses. RESULTS: Correlation of radiation dermatitis (RTOG scale) with the observed increased expression of Ki67, ATM, iNOS, HIF-1a and aGluc, failed to reach statistical significance when skin type and/or body weight were considered. Network interactions of proteins involved in tumor growth (Ki67, ATM) and/or affect the oxidation state of the cell (HIF-1a, iNOS, aGluc) were revealed, that may contribute to the risk of developing acute radiation dermatitis. CONCLUSION: Correlation of the increased expression of the studied proteins and the occurrence and severity of radiation dermatitis in women undergoing postoperative radiotherapy, failed to reach statistical significance. Pathway and network analyses predicted that vasodilation and angiogenesis may contribute to radiation-induced dermatitis via mechanisms that need to be further explored. Our strategy serves as a paradigm for coupling histopathological data to molecular findings and network analyses for risk assessment in the clinic. Copyright
Authors: Edwin A Robledo; Juan Murillo; Raquel Veiga Martin; Kevin Leiva; Corina Beiner; Maria Amelia Rodrigues; Marcio Fagundes; Joseph Panoff; Michael Chuong; Wensong Wu; Anuradha Godavarty Journal: Front Oncol Date: 2022-07-08 Impact factor: 5.738