Transcription factor immunohistochemistry in the diagnosis of pituitary tumours

Abstract

Objective: The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours. Methods: This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent’s Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the “histological cohort”. Patients with at least 12 months of post-surgical follow up were included in the subgroup “clinical cohort”. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of identifying “higher risk” histological subtypes was assessed. Results: There were 171 patient tumour samples analyzed in the histological cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 20/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher risk histological subtype tumours. These were associated with tumour invasiveness (p=0.050), early recurrence (12-24 months, p=0.013), shorter median time to recurrence (49 [IQR 22.5-73.0] v 15 [IQR 12.0-25.0] months, p=0.005) and reduced recurrence-free survival (p=0.031). Conclusions: Application of transcription factor analysis, in addition to hormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an improved approach to prognostication.

Classificazione e nomenclatura dei tumori neuroendocrini dell’ipofisi anteriore

“…Va sottolineato, però, che una diagnosi basata esclusivamente sui FT può essere fuorviante [2][3][4]8]. Un recente studio di Neou e colleghi [9] ha fornito una descrizione genetica ed epigenetica completa dei vari tipi e sottotipi dei tumori neuroendocrini dell'ipofisi anteriore, tutti con un'accurata caratterizzazione clinica e patologica.…”

Development of a cost-effective diagnostic algorithm incorporating transcription factor immunohistochemistry in the evaluation of pituitary tumours

“…1 ). Adoption of transcription factor analysis has been associated with improved diagnostic and prognostic information, including refinement of classification and improved identification of hormonally silent or ‘whispering’ tumours [ 2 – 5 ]. The recent release of the fifth edition of the WHO classification (2022) builds upon the transcription factor-based classification of pituitary tumours with description of new types, summarised in Table 1 [ 6 ].…”

“…However, the expansion of diagnostic IHC is also associated with increased cost and burden of work for laboratory staff [ 2 , 6 ]. Clinical and economic feasibility pose the need for a tiered approach [ 6 – 8 ].…”

“…We propose a tiered algorithm that builds on that of McDonald et al, utilising transcription factor IHC as the first step in accurate and efficient diagnosis of tumours. We compare this to the current “Gold Standard”, which is clinical evaluation in combination with a full panel of transcription factor and pituitary hormone IHC [ 2 ].…”

Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis

“…Immunohistochemistry with antibodies towards pituitary TFs has not yet been routinely implemented at many diagnostic laboratories, thus, pituitary cell-lineage based classification of PitNETs has not yet been validated in the clinical settings, except in one recent study [ 21 ]. Studies exploring how gene expression in PitNETs reflect the current classification in well-characterized tumor cohorts are limited [ 35 , 47 ].…”