Artikel
Claudin-1 downregulation plays a major role in the pathophysiology of invasive pituitary macroadenomas
Die Claudin-1-Downregulation spielt eine wichtige Rolle in der Pathophysiologie invasiver Hypophysen-Makroadenome
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Autoren
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Malte Mohme
- Universitätsklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie, Hamburg, Deutschland
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Roman Rotermund
- Universitätsklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie, Hamburg, Deutschland
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Klaus Christian Mende
- Universitätsklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie, Hamburg, Deutschland
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Till Burkhardt
- Friedrich-Ebert-Krankenhaus Neumünster, Neurochirurgie, Neumünster, Deutschland
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Jakob Matschke
- Universitätsklinikum Hamburg-Eppendorf, Institut für Neuropathologie, Hamburg, Deutschland
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Manfred Westphal
- Universitätsklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie, Hamburg, Deutschland
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Jörg Flitsch
- Universitätsklinikum Hamburg-Eppendorf, Klinik für Neurochirurgie, Hamburg, Deutschland
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Wolfgang Saeger
- Universitätsklinikum Hamburg-Eppendorf, Institut für Neuropathologie, Hamburg, Deutschland
| Veröffentlicht: | 26. Juni 2020 |
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Gliederung
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Objective: Pituitary adenomas are generally completely resectable, and thus can be cured. However, certain adenomas are invasive and complete resection is difficult. Until now it is unclear, which phenotype leads to invasion into the cavernous sinus. We hypothesize that the expression of Claudin-1 could play a role in the pathophysiology of invasive macroadenomas.
Methods: We prospectively collected tissue from 120 patients with invasive or non-invasive macroadenomas of the pituitary. When available, differential tissue analysis from the peripheral and central tumor areas was performed. Tumor tissue was evaluated for Claudin-1, a tight junction molecule, expression and Ki-67 index. Invasiveness was evaluated by the surgeon’s intraoperative assessment and radiological finding, as defined by the Knosp Score.
Results: We included 32 cases of acromegaly (78.1% invasive), 71 hormone inactive adenomas (HIA) (63.4% invasive), seven with cushing adenomas (57.1% invasive) and 10 prolactinomas (20% invasive) (p<0.001). Radiologically tumors presented in 15.4% with Knosp °I, 35.9% °II, 29.1% °III and 19.6% °IV.
We found a negative correlation for peripheral Claudin-1 expression with higher Knosp Grades (°III and °IV, p = 0.02). Knosp °I-II Claudin-1 positivity was (+) in 27.3%; (++) in 31.8% and (+++) in 40.9% of cases. Knosp °III-IV Claudin positivity was (+) in 51.4%; (++) in 35.1% and (+++) in 13.5%. Peripheral Claudin-1 positivity was associated with a higher grade of resection, as 40.9% Claudin-1 (+++) tumors and 31.8% of Claudin-1 (++) tumors could be completely resected, opposed to 46.7% of Claudin-1 (+) tumors in incomplete resection (p = 0.03). The same was found for the histological diagnosis of invasiveness in hormone HIA, which was also inversely correlated with Claudin-1 positivity (p = 0.02). There was no significant difference in tumor volume concerning claudin positivity. Intraoperative evaluation of invasiveness was inversely correlated with Claudin positivity as was radiological evaluation of invasiveness (p = 0.01).
Conclusion: Claudin-1 expression was inversely correlated to the invasiveness of pituitary macroadenomas. Our study supports the hypothesis, that a dysregulation of cell-cell adhesion contributes to the invasive nature of invasive pituitary macroadenomas. Claudin-1 expression should be assessed in larger cohorts in order to assess its impact on the outcome of macroadenomas.
