Is it time to consider the expression of specific-pituitary hormone genes when typifying pituitary tumours?

Araceli García-Martínez,Cristina Lamas,Rosa Cámara,Antonio Picó,Johana Sottile,Ignacio Aranda,Hernán Sandoval,Pedro Riesgo,Carmen Fajardo,Juan Antonio Simal,Raul M Luque

doi:10.1371/journal.pone.0198877

Abstract

The aim of the present study is to check whether we can replicate, in an independent series, previous results showing that the molecular study of pituitary-specific gene expression complements the inmunohistochemical identification of pituitary neuroendocrine tumours. We selected 112 patients (51 (46.4%) women; mean age 51.4±16 years; 102 macroadenomas (91.9%), 9 microadenomas (8.1%)) with complete clinical, radiological, immunohistochemical and molecular data from our data set of pituitary neuroendocrine tumours. Patients were different from those previously studied. We measured the expression of the pituitary-specific hormone genes and type 1 corticotrophin-releasing hormone and arginine vasopressin 1b receptors, by quantitative real-time polymerase chain reaction using TaqMan probes. Afterwards, we identified the different pituitary neuroendocrine tumour subtypes following the 2017 World Health Organization classification of pituitary tumours, calculating the concordance between their molecular and immuhistochemical identification. The concordance between molecular and immunohistochemical identification of functioning pituitary neuroendocrine tumours with the clinical diagnosis was globally similar to the previous series, where the SYBR Green technique was used instead of TaqMan probes. Our results also corroborated the poor correlation between molecular and immunohistochemical detection of the silent pituitary neuroendocrine tumour variants. This discrepancy was more remarkable in lactotroph, null-cell and plurihormonal pituitary neuroendocrine tumours. In conclusion, this study validates the results previously published by our group, highlighting a complementary role for the molecular study of the pituitary-specific hormone genes in the typification of pituitary neuroendocrine tumours subtypes.

Highlights

In 2017, the World Health Organization (WHO) classification of tumours of the pituitary gland superseded its previous 2004 version[1]
When the tumour showed dominant gene expression or immunoreactivity for more than one pituitary hormone coming from the same pituitary transcription factor, i.e. GH/PRL/ TSH, we considered the tumour as plurihormonal PIT1 (PH-PIT1) pituitary neuroendocrine tumour (PitNET)
When the tumour showed dominant gene expression or immunoreactivity for more than one pituitary hormone coming from different pituitary transcription factors, i.e. ACTH/GH, ACTH/PRL, follicle stimulating hormone (FSH)/PRL, we considered the tumour as an unusual plurihormonal (U-PH) PitNET

Summary

Introduction

In 2017, the World Health Organization (WHO) classification of tumours of the pituitary gland superseded its previous 2004 version[1]. Despite the great progress made in immunohistochemistry (IHC), this technique continues to rely on the skills of the observer, the antibodies used, and on the protein expression of the tumour cells. It insufficiently identified null cell tumours (NC) and plurihormonal (PH) tumours. It insufficiently predicted the clinical behaviour of atypical neoplasm subtypes, giving rise to proposals for a new terminology of the anterior pituitary neoplasms: pituitary neuroendocrine tumour (PitNET)[2]

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Conclusion