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Invasiveness, SOX2 Expression, and Resection Outcomes in TF-Defined PitNETs After Extra-Pseudocapsular Resection
Xing-Bo Li1,2, Kuo Zeng1,2, Xue-Yan Wan2
1Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Current Medical Science
|August 3, 2026
Summary
The new transcription factor (TF)-defined lineage system enhances pituitary neuroendocrine tumor (PitNET) classification. The PIT1-GH/PRL subgroup shows aggressive invasive features, with SOX2 positivity linked to higher hormone levels and lower resection rates.
Area of Science:
- Endocrinology and Oncology
- Molecular Pathology of Pituitary Tumors
Background:
- Pituitary neuroendocrine tumors (PitNETs) classification traditionally relies on hormone secretion and morphology.
- Transcription factor (TF)-defined molecular lineages offer a more precise approach to understanding PitNET heterogeneity.
Purpose of the Study:
- To investigate the relationship between TF-defined molecular lineages and the clinical characteristics of PitNETs.
- To assess the diagnostic precision and clinical utility of the 2022 WHO TF-defined lineage system in PitNETs.
Main Methods:
- Retrospective analysis of 274 patients undergoing transsphenoidal resection for PitNETs.
- Tumor classification based on TF-defined lineage, invasion grade, and Knosp score.
- Hierarchical multivariable logistic regression used to identify predictors of gross total resection (GTR).
Main Results:
- TF-defined lineage classification improved diagnostic precision, assigning definitive lineage in 74.7% of hormone-immunonegative tumors.
- The PIT1-GH/PRL subgroup exhibited the highest invasion grade and lowest GTR rate (58.3%); SOX2 positivity was frequent (41.7%).
- SOX2 positivity correlated with elevated preoperative ACTH and GH levels and was observed in multilineage and recurrent tumors.
Conclusions:
- The 2022 WHO TF-defined lineage system enhances PitNET diagnostic precision and aids in interpreting differentiation and molecular pathology.
- The PIT1-GH/PRL subgroup displays more aggressive invasive characteristics.
- Further validation is needed for SOX2 positivity in recurrent PitNETs due to limited cohort size.
