PURPOSE: To identify, using tissue microarray (TMA), an immunohistochemical panel predictive of response to ionizing radiation (IR) in rectal cancer. METHODS: TMA constructs were prepared from archived stage II/III rectal tumors and matching adjacent mucosa (n=38) from patients treated with pre-operative chemoradiation. Immunohistochemistry (IHC) was performed for MIB, Cyclin E, p21, p27, p53, survivin, Bcl-2, and BAX. Immunoreactivity along with clinical variables was subjected to univariate and forward stepwise logistic regression analyses. RESULTS: Pathological complete response (pCR) was 23.9%. The number of positive lymph nodes obtained in the resected specimen was associated with pCR. Immunoreactivity for MIB (Sn 15%, Sp 65%, OR 0.33), p53 (Sn 3%, Sp 84%, OR 0.16), Bcl-2 (Sn 11%, Sp 74%, OR 0.35), and BAX (Sn 92%, Sp 80%, OR 46) was associated with pathological response (all p's<0.001). Forward stepwise logistic regression analysis demonstrated that MIB was an independent predictor of a response to chemoradiation (p=0.001). CONCLUSIONS: A combined panel of mediators of apoptosis alone or combined with clinical factors is a feasible approach that can be applied to rectal tumor biopsies to predict a response to chemoradiation. The most sensitive factor was BAX; while MIB independently predicted a response to chemoradiation. Published by Elsevier Ltd.
PURPOSE: To identify, using tissue microarray (TMA), an immunohistochemical panel predictive of response to ionizing radiation (IR) in rectal cancer. METHODS: TMA constructs were prepared from archived stage II/III rectal tumors and matching adjacent mucosa (n=38) from patients treated with pre-operative chemoradiation. Immunohistochemistry (IHC) was performed for MIB, Cyclin E, p21, p27, p53, survivin, Bcl-2, and BAX. Immunoreactivity along with clinical variables was subjected to univariate and forward stepwise logistic regression analyses. RESULTS: Pathological complete response (pCR) was 23.9%. The number of positive lymph nodes obtained in the resected specimen was associated with pCR. Immunoreactivity for MIB (Sn 15%, Sp 65%, OR 0.33), p53 (Sn 3%, Sp 84%, OR 0.16), Bcl-2 (Sn 11%, Sp 74%, OR 0.35), and BAX (Sn 92%, Sp 80%, OR 46) was associated with pathological response (all p's<0.001). Forward stepwise logistic regression analysis demonstrated that MIB was an independent predictor of a response to chemoradiation (p=0.001). CONCLUSIONS: A combined panel of mediators of apoptosis alone or combined with clinical factors is a feasible approach that can be applied to rectal tumor biopsies to predict a response to chemoradiation. The most sensitive factor was BAX; while MIB independently predicted a response to chemoradiation. Published by Elsevier Ltd.
Authors: L Flanagan; A U Lindner; C de Chaumont; J Kehoe; J Fay; O Bacon; S Toomey; H J Huber; B T Hennessy; E W Kay; D A McNamara; J H M Prehn Journal: J Mol Med (Berl) Date: 2014-11-13 Impact factor: 4.599
Authors: L Flanagan; J Kehoe; J Fay; O Bacon; A U Lindner; E W Kay; J Deasy; D A McNamara; J H M Prehn Journal: Radiat Oncol Date: 2015-06-13 Impact factor: 3.481