TGFBR3L—An Uncharacterised Pituitary Specific Membrane Protein Detected in the Gonadotroph Cells in Non-Neoplastic and Tumour Tissue

• Main Authors: Evelina Sjöstedt, Anders J. Kolnes, Nicoleta C. Olarescu, Nicholas Mitsios, Feria Hikmet, Åsa Sivertsson, Cecilia Lindskog, Kristin A. B. Øystese, Anders P. Jørgensen, Jens Bollerslev, Olivera Casar-Borota
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Cancers
• Subjects: gonadotroph cells; pituitary gland; pituitary neuroendocrine tumours; membrane protein; immunohistochemistry; hormone secretion
• Online Access: https://www.mdpi.com/2072-6694/13/1/114

Here, we report the investigation of transforming growth factor beta-receptor 3 like (TGFBR3L), an uncharacterised pituitary specific membrane protein, in non-neoplastic anterior pituitary gland and pituitary neuroendocrine tumours. A polyclonal antibody produced within the Human Protein Atlas project (HPA074356) was used for TGFBR3L staining and combined with SF1 and FSH for a 3-plex fluorescent protocol, providing more details about the cell lineage specificity of TGFBR3L expression. A cohort of 230 pituitary neuroendocrine tumours were analysed. In a subgroup of previously characterised gonadotroph tumours, correlation with expression of FSH/LH, E-cadherin, oestrogen (ER) and somatostatin receptors (SSTR) was explored. TGFBR3L showed membranous immunolabeling and was found to be gonadotroph cell lineage-specific, verified by co-expression with SF1 and FSH/LH staining in both tumour and non-neoplastic anterior pituitary tissues. TGFBR3L immunoreactivity was observed in gonadotroph tumours only and demonstrated intra-tumour heterogeneity with a perivascular location. TGFBR3L immunostaining correlated positively to both FSH (<i>R</i> = 0.290) and LH (<i>R</i> = 0.390) immunostaining, and SSTR3 (<i>R</i> = 0.315). TGFBR3L correlated inversely to membranous E-cadherin staining (<i>R</i> = −0.351) and oestrogen receptor β mRNA (<i>R</i> = −0.274). In conclusion, TGFBR3L is a novel pituitary gland specific protein, located in the membrane of gonadotroph cells in non-neoplastic anterior pituitary gland and in a subset of gonadotroph pituitary tumours.