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Purpose <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Oxidative phosphorylation patterns in pituitary adenoma/neuroendocrine tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月11日

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  • Maaia Margo Jentus,
  • René 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

摘要

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.