Prognostic value of GRIM-19, NF-kappa B and IKK2 in patients with high-grade serous ovarian cancer
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2018
Autores
Ilelis, Felipe
do Amaral, Nayra Soares
Alves, Mariana Rezende
Balieiro Anastacio da Costa, Alexandre Andre
Calsavara, Vinicius Fernando
Lordello, Leonardo
De Brot, Louise
Soares, Fernando Augusto
Rodrigues, Iara Sant'Ana
Rocha, Rafael Malagoli [UNIFESP]
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Aims: High grade serous carcinoma (HGSC) is an aggressive tumour, and most patients relapse after treatment, acquiring resistance to platinum-based chemotherapy. One of the resistance mechanisms proposed is apoptosis evasion triggered by drug-related cytotoxic effect in the cell. In this context, this study aims to evaluate the protein expression of GRIM-19, NF-kappa B and IKK2, their association with chemotherapy response and to determine their prognostic values in HGSC. & para;& para;Methods: GRIM-19, NF-kappa B and IKK2 expression was evaluated by immunohistochemistry (IHC) in 71 patients with HGSC selected between 2003 and 2013, whose underwent primary debulking surgery with complete cytoreduction. Protein expression was analyzed in relation to platinum response groups, tumour progression, clinicopathological data and survival. & para;& para
Results: Positive IKK2 expression was related to resistance (p = 0.011), shorter disease-free survival (p = 0.001) and overall survival (p = 0.026) and was also a risk factor for relapse (p = 0.002) and death (p = 0.032). The association between IKK2 and NF-kappa B positivity predicted a subgroup with shorter overall survival (p = 0.004), disease-free survival (p = 0.003) and resistance to platinum-based chemotherapy (p = 0.036). NF-kappa B positivity was associated with worse overall survival (p = 0.005) and disease-free survival (p = 0.027) and was a positive predictor for relapse (p = 0.032) and death (p = 0.008). Higher expression of GRIM-19 was associated with higher disease-free survival (p = 0.039) and was a negative predictor for relapse (p = 0.046). & para;& para;Conclusions: GRIM-19 is a potential predictor of prognosis and disease recurrence in HGSC. IKK2 and NF-kappa B are related to poor prognosis and are potential predictors of response to platinum-based chemotherapy in HGSC. IHC analyses of GRIM19, IKK2 and NF-kappa B may be important in the attempt to provide prognostic values for relapse and response to treatment in patients with HGSC.
Results: Positive IKK2 expression was related to resistance (p = 0.011), shorter disease-free survival (p = 0.001) and overall survival (p = 0.026) and was also a risk factor for relapse (p = 0.002) and death (p = 0.032). The association between IKK2 and NF-kappa B positivity predicted a subgroup with shorter overall survival (p = 0.004), disease-free survival (p = 0.003) and resistance to platinum-based chemotherapy (p = 0.036). NF-kappa B positivity was associated with worse overall survival (p = 0.005) and disease-free survival (p = 0.027) and was a positive predictor for relapse (p = 0.032) and death (p = 0.008). Higher expression of GRIM-19 was associated with higher disease-free survival (p = 0.039) and was a negative predictor for relapse (p = 0.046). & para;& para;Conclusions: GRIM-19 is a potential predictor of prognosis and disease recurrence in HGSC. IKK2 and NF-kappa B are related to poor prognosis and are potential predictors of response to platinum-based chemotherapy in HGSC. IHC analyses of GRIM19, IKK2 and NF-kappa B may be important in the attempt to provide prognostic values for relapse and response to treatment in patients with HGSC.
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Pathology Research And Practice. Jena, v. 214, n. 2, p. 187-194, 2018.