How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

María Eugenia Torregrosa-Quesada,Araceli García-Martínez,Antonio Picó,Rosa Cámara,Sebastián Martínez-López,Cristina Lamas,Sandra Silva-Ortega,Ignacio Aranda,Carmen Fajardo

doi:10.3390/cancers11121990

Abstract

The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.

Highlights

The World Health Organization (WHO) Classification of Tumors of Endocrine Organs, in its fourth edition, bases the classification of pituitary tumors on specific transcription factors, namely, pituitary-specific positive transcription factor 1 (Pit-1), Tbox family member TPIT (Tpit), and steroidogenic factor 1 (SF-1), involved in the differentiation of anterior pituitary cells [1]
Cancers 2019, 11, x factors in 251 pituitary neuroendocrine tumors (PitNETs) previously categorized in subtypes according to their pituitary-specific hormone gene profile
Data have shown that GATA2 is detected in the gonadotropin subunit-positive tumors and in most thyrotroph tumors (TT) [15]. These results suggest that the interaction between GATA2 and Pit-1 could promote the differentiation of TTs

Summary

Introduction

The World Health Organization (WHO) Classification of Tumors of Endocrine Organs, in its fourth edition, bases the classification of pituitary tumors on specific transcription factors, namely, pituitary-specific positive transcription factor 1 (Pit-1), Tbox family member TPIT (Tpit), and steroidogenic factor 1 (SF-1), involved in the differentiation of anterior pituitary cells [1]. Pituitary neuroendocrine tumors (PitNETs), as they have been recently named [2], have increased in frequency mainly as a result of the exponential increase in cranial imaging techniques. A meta-analysis of 33 articles based on autopsy and radiological data showed that the prevalence of PitNETs ranged from 1% to 40% in the imaging studies, with similar results in the postmortem studies. A nationwide study showed a prevalence of pituitary tumors of 115.57/100,000, with On the basis of these data, the authors estimated an overall prevalence of PitNETs of 16.7% in the general population [3].

Methods

Results

Discussion

Conclusion