SFEBES2021 Oral Communications Reproductive and Neuroendocrinology (6 abstracts)
Hyper-phosphorylation of β-catenin at Serine552 correlates with invasion and predicts recurrence of Non-Functioning Pituitary Tumours (NFPTs)
Ashutosh Rai 1,2 , Soujanya D. Yelamanchi 3 , Bishan D Radotra 2 , Sunil K Gupta 2 , Rajesh Chhabra 2 , Akhilesh Pandey 4 , Márta Korbonits 1 , Carles Gaston-Massuet 1 & Pinaki Dutta 2
1Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; 2Postgraduate Institute of Medical Education and Research, Chandigarh, India; 3Indian Institute of Science, Bangalore, India; 4Institute of Genetic Medicine, and the division of Proteomics, Mayo Clinic, Rochester, Minnesota, USA
Background: No predictive biomarkers for NFPT recurrence have been identified, apart from Ki67. We employed high-throughput mass spectrometry-based analyses to examine the phosphorylation pattern of different subsets of NFPTs.
Methods: Based on histopathological, radiological and surgical features, NFPTs were sub-grouped into three groups: non-invasive (n = 15), invasive (n = 10) and recurrent (n = 5) subtypes. Invasiveness was determined by radiology (Knosp classification 3&4), histopathological invasion (bone, dura and mucosa) and intraoperative findings. Tumour recurrence was based on radiological data for a mean follow-up of 10y (SD±5.4y). Proteins were extracted from frozen tissues, phosphopeptides enriched using TiO2 and labelled with tandem mass tags and subjected mass spectrometry (Orbitrap) for quantification. Candidate hyper-phosphorylated proteins were validated in NFPTs by immunohistochemistry (n = 200) on tissue microarray and immunoblotting (n = 36).
Results: Out of 3185 identified phosphopeptides, phospho-serine showed the highest level of difference (90.3%) among the tumour subtypes, followed by threonine (8.9%) and tyrosine (0.8%). One of the identified group of phosphoproteins with subtype-specific expression pattern was Ser552 of β-catenin showing significant hyper-phosphorylation in recurrent (P < 0.001) and invasive (P < 0.001) NFPTs. We performed receiver operating characteristics curve analysis to find the optimal cut-off value of β-catenin pSer552 H-score in patients who had recurrence (n = 44) or non-recurrence (n = 156) and observed an area under curve of 0.717 (95% CI: 0.610-0.797), indicating a good prognostic ability of the β-catenin pSer552H-score. A cut-off value of 160 for the β-catenin pSer552 H-score gives a sensitivity of 68.8% and a specificity of 72.6% for tumour recurrence. Kaplan-Meier survival curve analysis shows strong statistical correlation in the recurrence free survival (P < 0.0001) and the nuclear positive staining of β-catenin pSer552 with a hazard ratio of 3.1 (95% CI 1.5-6.3).
Conclusion: Our results suggest that the phosphorylation status of β-catenin at Ser552 could act as predictive biomarker of tumour recurrence and invasion in NFPTs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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