PD-L1-Positive High-Grade Triple-Negative Breast Cancer Patients Respond Better to Standard Neoadjuvant Treatment-A Retrospective Study of PD-L1 Expression in Relation to Different Clinicopathological Parameters.

Triple negative breast cancer (TNBC) is typically a high-grade breast cancer with poorest clinical outcome despite available treatment modalities with chemo-, immuno- and radiotherapy. The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor closely related to programmed death ligand 1 (PD-L1) expressed on T lymphocytes modulating antitumor immunity. Immune-checkpoint inhibitors (ICI) are showing promising results in a subset of breast cancer patients in both neo- and adjuvant settings. Pathologic complete response (pCR) after neoadjuvant treatment was found to be associated with better prognosis. We analyzed the prognostic and predictive significance of PD-L1 (SP142 assay) immunohistochemical expression on TNBC patients' samples as illustrated by pCR with regard to its relation to treatment regimen, stage, BRCA mutational status and outcome. Furthermore, we analyzed a few other clinicopathological parameters such as age, TILs and proliferation index. The study highlighted a positive role of PD-L1 evaluation for personalized pCR probability assessment. Although considerable research was made on comparison of PD-L1 level in TNBC with different patient parameters, to our best knowledge, the relation of PD-L1 status to pCR while taking treatment regimen and stage into consideration was so far not investigated

Small Biopsy Samples: Are They Representative for Biphenotypic Sinonasal Sarcoma?

(1) Background: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade neoplasm of the sinonasal tract. It is characterized by specific PAX3 gene rearrangements and both myogenic and neural differentiation. The purpose of the study was to describe the histologic, immunohistochemical and molecular features of BSNS and indicate important clues for small incisional biopsy diagnostics. (2) Methods: Archival samples from patients with nasal cavities or ethmoid sinuses tumors were searched for BSNS cases. Inclusion criteria were the presence of spindle cell morphology and low-grade appearance. Both biopsy and resection specimens were stained for identical IHC panels including, i.a., S100, SMA, SOX10 and PAX3. FISH for PAX3 and SS18 was performed on biopsy specimens. (3) Results: BSNS diagnosis was made in 6 cases included in the study and confirmed by PAX3 rearrangement by FISH in 5 specimens. The pattern of IHC expression was identical for paired biopsy and resection samples apart from one BSNS case. (4) Conclusions: Incisional biopsy seems to be a sufficient method to establish BSNS diagnosis in most cases. Characteristic morphological features together with S100, SOX10 and SMA as the screening markers are useful for confirming the diagnosis. In cases of divergent morphology and immunoprofile evaluation of PAX3 rearrangement is vital

The Role of Pathology-Based Methods in Qualitative and Quantitative Approaches to Cancer Immunotherapy

Immune checkpoint inhibitors, including those concerning programmed cell death 1 (PD-1) and its ligand (PD-L1), have revolutionised the cancer therapy approach in the past decade. However, not all patients benefit from immunotherapy equally. The prediction of patient response to this type of therapy is mainly based on conventional immunohistochemistry, which is limited by intraobserver variability, semiquantitative assessment, or single-marker-per-slide evaluation. Multiplex imaging techniques and digital image analysis are powerful tools that could overcome some issues concerning tumour-microenvironment studies. This novel approach to biomarker assessment offers a better understanding of the complicated interactions between tumour cells and their environment. Multiplex labelling enables the detection of multiple markers simultaneously and the exploration of their spatial organisation. Evaluating a variety of immune cell phenotypes and differentiating their subpopulations is possible while preserving tissue histology in most cases. Multiplexing supported by digital pathology could allow pathologists to visualise and understand every cell in a single tissue slide and provide meaning in a complex tumour-microenvironment contexture. This review aims to provide an overview of the different multiplex imaging methods and their application in PD-L1 biomarker assessment. Moreover, we discuss digital imaging techniques, with a focus on slide scanners and software