Forschung & Innovation
Publikationen
Oxidative phosphorylation patterns in pituitary adenoma/neuroendocrine tumors
PMU Autor*innen
Rene G. Feichtinger, Sara Huber, Laura Ebner, Johannes A. Mayr
Alle Autor*innen
Maaia Margo Jentus, Rene G. Feichtinger, Willem E. Corver, Sara Huber, Laura Ebner, Iris Pelsma, Leontine Bakker, Wouter Van Furth, Marco Verstegen, Nienke Biermasz, Johannes A. Mayr, Hans Morreau
Fachzeitschrift
Pituitary
Kurzfassung
Purpose Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, exhibit marked lineage-specific heterogeneity. The underlying molecular biology of certain tumor/adenoma types, particularly gonadotroph tumors/adenomas (SF1-lineage) - which typically exhibit stable genomes - remains poorly understood. This study aimed to define expression patterns of oxidative phosphorylation (OXPHOS) system subunits across PitNET/adenoma lineages. Methods Immunohistochemistry was performed in 43 previously molecularly and histologically classified PitNETs/adenomas on tumor and normal adenohypophyseal tissue for VDAC1 (porin) to assess mitochondrial density and the expression of OXPHOS-subunits. Quantified staining intensity scores were used for statistical analyses, and mtDNA sequencing was successful in 21 tumors/adenomas. Results Mitochondrial density was significantly increased in PitNETs/adenomas compared with normal tissue. Alterations in OXPHOS subunits expression were non-uniform: complex I deficiency was the most frequent abnormality, often associated with disruptive mtDNA mutations, particularly in genomically stable gonadotroph tumors/adenomas. Two corticotroph tumors/adenomas with near-haploid genomes also harboured disruptive complex I mutations. Alterations in other complexes were less common and typically occurred in combination. Staining heterogeneity was frequent (24/43 tumors/adenomas), including focal expression loss, especially in SF1-lineage and all mtDNA-mutated tumors/adenomas, but also present in tumors/adenomas without mtDNA mutations. Conclusions PitNETs/adenomas display lineage-specific and highly heterogeneous OXPHOS-system phenotypes. Complex I deficiency and mtDNA mutations occur not only in genomically stable gonadotroph tumors/adenomas but also in highly disrupted corticotroph tumors/adenomas with a near-haploid genome. Further studies including sequencing of nuclear-encoded OXPHOS-related genes are required to clarify the contribution of altered OXPHOS-subunit expression to PitNET/adenoma biology and potential clinical applications.
Keywords
CELLULAR RESPIRATION, Oxidative Phosphorylation, Electron transport chain, PitNET, Pituitary adenoma