Systematic review of the molecular basis for cavernous sinus invasion in somatotropinomas

Clinical Snapshot

Key Findings

• P Value: Not reported for pooled analysis

• Effect Size: Not quantified - qualitative synthesis only

• Primary Outcome: Molecular markers associated with cavernous sinus invasion in somatotropinomas

• Nnt Or Sensitivity: Four main molecular pathways identified: epithelial-mesenchymal transition, cellular proliferation, hormonal signalling, and tumour angiogenesis

• Confidence Interval: Not reported

Clinical Application

Molecular markers could inform pre-operative planning and prognostication, but require validation in larger prospective studies Relevant to Australian neurosurgical and endocrinology practice; molecular testing may require PBS consideration for future biomarker development Adult patients with growth hormone-secreting pituitary adenomas requiring surgical intervention

Abstract

Somatotropinomas are a subtype of pituitary adenomas that have a particular predilection to invade the cavernous sinus. The objective of this systematic review was to examine the evidence regarding the molecular basis for cavernous sinus invasion in somatotropinomas. This review was conducted in accordance with the 2020 PRISMA guidelines on 13 April 2025. Inclusion criteria were reports of associations between somatotropinoma molecular changes and cavernous sinus invasion in adult patients. Title/abstract screening and full-text screening were performed, with studies assessed for risk of bias using the Newcastle-Ottawa scale. A total of 43 studies were identified, encompassing 1,824 patients (724 invasive tumours). Overall, 33 studies identified molecules that were upregulated in invasive tumours and 20 studies identified molecules that were downregulated. Few studies incorporated modern proteomic or transcriptomic techniques. Risk of bias was low with a mean Newcastle-Ottawa scale score of 7.0 (±0.6). Molecules associated with invasion were related to epithelial-mesenchymal transition (E-cadherin, ESRP1, fascin-1, and MMP-9), cellular proliferation (PTTG, AIP, TCERG1, EIF2β, E2F1, Notch 2, STAT3, ARRB1, TGFB1, SMAD3, SOX9, SGK1, MAGEA6 DLL3, EGFL7, and pEGFR), hormonal signalling (GNAS, DRD5, DRD1, sst5TMD4, SSTR2, and SSTR5), and tumour angiogenesis (VEGF and Drp1). These molecular variations present a possible explanation for the proclivity of somatotropinomas for the cavernous sinus. Identified molecules represent options for novel targeted therapies or biomarkers that could inform prognostication. Modern proteomic and transcriptomic techniques and larger somatotropinoma datasets are required to further elucidate the molecular pathways responsible for cavernous sinus invasion in somatotropinomas.

References

1. 1.Ovenden, C. D., Candy, N., Bacchi, S., Sorvina, A., Castle-Kirszbaum, M., Poonnoose, S., Vrodos, N., Jukes, A., Santoreneos, S., Torpy, D. J., Psaltis, A., & De Sousa, S. (2026). Systematic review of the molecular basis for cavernous sinus invasion in somatotropinomas. Endocrine-Related Cancer. https://doi.org/10.1530/ERC-25-0236