Microsatellite instability (MSI) has been identified in several tumors arising from either germline or somatic aberration. The presence of MSI in cancer predicts the sensitivity to immune checkpoint inhibitors (ICIs), particularly PD1/PD-L1 inhibitors. To date, the predictive role of MSI is currently used in the selection of colorectal cancer patients for immunotherapy; moreover, the expansion of clinical trials into other cancer types may elucidate the predictive value of MSI for non-colorectal tumors. In clinical practice, several assays are used for MSI testing, including immunohistochemistry (IHC), polymerase chain reaction (PCR) and next-generation sequencing (NGS). In this review, we provide an overview of MSI in various cancer types, highlighting its potential predictive/prognostic role and the clinical trials performed. Finally, we focus on the comparison data between the different assays used to detect MSI in clinical practice.

Background: Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers. Methods: Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS). Results: In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR. Conclusions: In clinical practice, MMR–IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC.

Background. Triple negative breast cancer (TNBC) is a heterogeneous group of tumors with early relapse, poor overall survival, and lack of effective treatments. Hence, new prognostic biomarkers and therapeutic targets are needed. Methods. The expression profile of all twenty-five human selenoproteins was analyzed in TNBC by a systematic approach.In silicoanalysis was performed on publicly available mRNA expression datasets (Cancer Cell Line Encyclopedia, CCLE and Library of Integrated Network-based Cellular Signatures, LINCS). Reverse transcription quantitative PCR analysis evaluated selenoprotein mRNA expression in TNBC versus non-TNBC and normal breast cells, and in TNBC tissues versus normal counterparts. Immunohistochemistry was employed to study selenoproteins in TNBC tissues. STRING and Cytoscape tools were used for functional and network analysis. Results.GPX1, GPX4, SELENOS, TXNRD1 and TXNRD3 were specifically overexpressed in TNBC cells, tissues and CCLE/LINCS datasets. Network analysis demonstrated that SELENOS-binding valosin-containing protein (VCP/p97) played a critical hub role in the TNBCselenoproteins sub-network, being directly associated with SELENOS expression. The combined overexpression of SELENOS and VCP/p97 correlated with advanced stages and poor prognosis in TNBC tissues and the TCGA dataset. Conclusion. Combined evaluation of SELENOS and VCP/p97 might represent a novel potential prognostic signature and a therapeutic target to be exploited in TNBC.

Background: Lung cancer remains the leading cause of cancer-related mortality, often diagnosed at advanced stages, where minimally invasive tissue sampling is essential for diagnosis and molecular profiling. Rapid On-Site Evaluation (ROSE) enhances the diagnostic yield of small biopsies, but is frequently limited by a shortage of pathologists and logistical constraints. Telepathology offers a potential solution by enabling remote real-time assessment. This study evaluates the feasibility, diagnostic accuracy, and efficiency of telecytology-assisted ROSE (TC-ROSE) using touch imprint cytology (TIC) during CT-guided transthoracic core needle biopsy (CNB) of pulmonary nodules. Methods: 50 patients underwent CNB. TIC samples were assessed and evaluated on-site or remotely via a fully remote-controlled microscope system (OCUS^®). TIC slide preparation was performed by pathologists (30 cases), radiologists (10), and trained assistants (10). The study analyzed diagnostic concordance between remote and on-site assessments, time efficiency, and the feasibility of involving non-pathologists in TIC preparation. Results: Diagnostic samples were obtained in 86% of TIC samples, with full concordance (100%) between TC-ROSE and traditional ROSE. The slides required approximately 140 s for scanning, and the overall evaluation time was around 3 min per case. Overall, 100% of TICs were adequately assessed by both pathologists and non-pathologists. No increased number of complications was recorded among patients with TCROSE, compared to those ROSE evaluated. The remote setup allowed pathologists to maintain routine workflows, improving time efficiency. Conclusions: The findings confirm that telecytology is a viable, accurate, and efficient approach to ROSE, offering a practical solution for overcoming workforce and logistical barriers, particularly in settings with limited pathology resources.

In clinical practice, breast cancer (BC) diagnosis traditionally relies on morphological analysis and the immunohistochemical (IHC) expression of markers s