HSP27, gamma H2AX and 53BP1 as predictive/prognostic factors in cancer patients treated with platinum compounds

VILCHEZ ARUANI J; CUELLO CARRION FD; SEMINO S; IBARRA J.; FLORES LEYVA RJ; GARCÍA MBIA MB; GONZALEZ L; VARGAS ROIG LM; NADIN SB

Mendoza

Congreso; XXXVI Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2018

Sociedad de Biología de Cuyo

Over the past 30 years, platinum agents have been extensively used for the treatment of various solid tumors. Their main target is the DNA molecule, forming covalent DNA adducts, thereby inhibiting replication and transcription and inducing cell death. Resistance to platinum-based chemotherapy that some patients acquire during treatment, limits the scope of its full potential. The biochemical mechanisms related to such resistance are multifactorial, including tolerance to nuclear DNA damage and heat shock proteins (HSPs). HSP27 (HSPB1) is overexpressed in many cancer types and influences cellular processes such as apoptosis and DNA repair and has also been related to drug resistance. One of the first events in the activation of DNA damage repair pathway is phosphorylation of histone H2AX, yielding gammaH2AX foci, that recruits other factors such as 53BP1, an important mediator of DNA damage checkpoints. Our main objective was to determine the predictive/prognostic value of HSP27, gammaH2AX, 53BP1 and the DNA repair proteins, ERCC1, MLH1 and MSH2 in tumor biopsies from cancer patients who received platinum-based chemotherapy (cisplatin/carboplatin). Immunohistochemistry was employed to detect the expression of HSP27, gammaH2AX, 53BP1, ERCC1, MLH1 and MSH2 in paraffin-embedded tumor tissues from 31 cancer patients before chemotherapy (mean follow-up 11.7 months). Patients with complete clinical response to chemotherapy showed lower expression of cytoplasmic and nuclear HSP27 than patients with partial response, stable disease and progressive disease (P