TGFBR3L in Non-Functioning Pituitary Neuroendocrine Tumours

KA. øystese*^a (Dr), AJ. Kolnes^b (Dr), E. Sjøstedt^c (Dr), O. Nicoleta Cristina^a (Dr), A. Heck^d (Dr), CB. Olivera^e (Dr), J. Bollerslev^f (Prof), AP. Jørgensen^d (Dr)

^a Institute of Clinical Medicine, Faculty of Medicine, University of Oslo; Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, NORWAY ; ^b Institute of Clinical Medicine, Faculty of Medicine, University of Oslo; Section of Specialized Endocrinology, Oslo, NORWAY ; ^c Department of Neuroscience, Karolinska Institutet; Department of Immunology, Genetics and Pathology, Uppsala University, Stockholm, SWEDEN ; ^d Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, NORWAY ; ^e Department of Immunology, Genetics and Pathology, Uppsala University;Department of Clinical Pathology, Uppsala University Hospital,, Uppsala, SWEDEN ; ^f Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NORWAY

* kaoystes@medisin.uio.no

Background: Transforming Growth Factor Beta Receptor 3 Like (TGFBR3L) is a pituitary enriched gene that is selectively expressed in gonadotroph cells. We have recently shown in a retrospective material that TGFBR3L is present both in gonadotroph tumours and in normal gonadotroph cells. The protein has been found to be a coreceptor for inhibin B, involved in regulation of FSH and fertility in mouse studies. This study aimed to validate previous findings of TGFBR3L in non-functioning pituitary neuroendocrine tumours (NF-PitNETs).

Methods: 145 patients operated for clinically NF-PitNETs (116 gonadotroph) were included prospectively. The tumours were classified based on the presence of pituitary hormones and/or pituitary specific transcription factors. Immunohistochemical (IHC) staining for FSH and LH was scored using the immunoreactive score (IRS). TGFBR3L was scored based on the percentage of positive staining cells (negative: no positive cells; low: ≤10% positive staining cells; moderate: 10-30% positive staining cells; high: ≥ 30% positive staining cells), and compared to clinical and radiological data.

Results: Positive staining for TGFBR3L was present in 60 (52%) of the gonadotroph tumours. TGFBR3L was not detected in tumours of other lineages than the gonadotroph. Only four tumours showed positive staining for TGFBR3L in ≥10% of cells. The TGFBR3L positivity was not associated with gender, age at primary surgery, tumour invasiveness or preoperative tumour volume. TGFBR3L detection showed a positive correlation to the IRS of LH (ρ=0.56, p<0.001), but not to the IRS of FSH (ρ=0.15, p=0.15).

Conclusion: We have validated that TGFBR3L is selectively expressed in gonadotroph NF-PitNETs, and that there is an association with LH staining, as suggested in a retrospective study. The function of TGFBR3L in the gonadotroph NF-PitNETs is yet to be elucidated.

The author has declared no conflict of interest.