EVIDENCE OF DAMAGE RESPONSE ACTIVATION IN HUMAN PITUITARY NEUROENDOCRINE TUMOURS

FERNANDEZ, S; BERTETTI C; VENIER AC; BERNHARDT C; PAUTASO M; SOSA L DEL V.; GUTIÉRREZ, S; GRONDONA E; DE PAUL AL

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Senescence is considered to be a stress response characterized by permanent cell cycle arrest, which can be triggered by different factors including DNA damage, oxidative stress. This program may constitute a plausible explanation for the benign nature of pituitary neuroendocrine tumours (PitNETs). We analysed the oxidative stress response activation, as part of the senescent process, in human somatotroph and lactotroph PitNETs. Samples from female and male patients (n=15) were supplied by Clínica Reina Fabiola and Sanatorio Allende, Córdoba. Clinical records and GH, PRL and Ki-67 immunostaining were also provided. The 8-hydroxy-2’-deoxyguanosine (8OhdG) expression, a marker of oxidative damage in DNA, and Nuclear factor erythroid 2-related factor 2 (Nrf2), indicative of antioxidant response activation, were evaluated by immunohistochemistry. Five randomly chosen fields were selected (400x) and 1000 cells were counted. Data are expressed as percentages of nuclear 8OdHG positive cells in relation to total cell number. The cytoplasmic Nrf2 expression intensity was classified as weak/strong and focal/diffuse regarding its distribution. Statics analysis: t-Test.In somatotroph PitNETs, the positive cell number exhibiting 8OhdG nuclear expression was significantly higher when compared to lactotroph PitNETs (13.6% vs 5.4% respectively). Furthermore, in the first group, the cytosolic Nrf2 expression was predominantly strong and diffuse whereas in lactotroph PitNETs this signal showed a pattern exclusively weak and focal. In somatotroph and lactotroph PitNETs, there would be a disparity in the cellular stress response. Differences in marker expressions detected in human PitNETs expose the specificity of this cellular phenomenon to the tumour subtype. The highest antioxidant response, detected somatotrophs PitNET, to face the DNA oxidative damage, may suggest that cellular senescence could be a significant mediator to avoid unregulated cell proliferation in these tumours