Abstract
Generally, predictive biomarker tests are clinically validated on histological formalin-fixed, paraffin-embedded (FFPE) samples. In addition to FFPE samples, cytological samples have also emerged as a useful approach to detect predictive biomarkers. However, as of today, despite the promising results reported in the recent literature, their full implementation in routine clinical practice is still lagging owing to a lack of standardized preparatory protocols, challenging assessments of cyto-histological correlation, and variable inter-observer agreement. The aim of this report was to explore the possibility of implementing a large-scale validation of predictive biomarker testing on cytological material. To this aim, we evaluated the technical feasibility of PD-L1 assessment on a cell block (CB)-derived tissue microarray (cbTMA). Consecutive and unselected CBs prepared from metastatic lymph node fine-needle cytology (FNC) samples were retrospectively collected and used for TMA construction. PD-L1 immunohistochemistry (IHC) was carried out on cbTMA sections with the companion diagnostic kit SP263 assay. TMA contained 33 CB-derived cores. A total of 20 sections were hematoxylin and eosin (H&E) stained. Overall, 29 (88%) samples were visible at least in one H&E-stained slide. Four cases out of five sections stained with the SP263 assay (4/29, 13.8%) showed PD-L1 positivity in neoplastic and/or immune cells; remarkably, no unspecific background was observed. Although our study was based on a limited and non-selected series, our findings do provide proof of concept for the use of cbTMA in predictive biomarker testing on cytological material in large-scale post-clinical trial validation studies, multicenter studies, and quality control programs.
Highlights
In the last decade, molecular cytopathology has emerged as a very rapidly evolving field of predictive pathology, with an increasing number of molecular tests performed on a wide range of cytological preparations [1,2]
We retrospectively reviewed consecutive and unselected cell block (CB) prepared from fineneedle cytology (FNC) samples of metastatic lymph nodes; FNAs were performed at the Cytopathology Division of the University of Naples “Federico II”
Experiences carried out exclusively on fluid cytology demonstrated that TMAs are efficiently applicable to CB specimens
Summary
Molecular cytopathology has emerged as a very rapidly evolving field of predictive pathology, with an increasing number of molecular tests performed on a wide range of cytological preparations [1,2]. The high quality of nucleic acids extracted from cytological specimens and the steady upgrading of multiplexed, highly sensitive molecular assays with minimal nucleic acid input have all contributed to the ongoing development of molecular cytopathology [3,4,5,6] Despite such great advances in the field and the many advantages of cytological material, especially in hard-to-reach tumors, histological formalin-fixed and paraffin-embedded (FFPE) samples continue to prevail over cytological samples for the selection of targeted treatments. The persistent paucity of cytological testing in routine pathology practice is largely due to a few unmet analytical challenges affecting the whole gamut of the analytical phases Among these are a lack of homogeneous tissue handling and processing protocols, discrepant cyto-histological correlation, and interpretation of results. Unless these challenges are met through the careful validation of predictive biomarker testing on cytological material, this excellent resource will most likely continue to remain underused
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