Inter-Assay Variability of TROP2 Immunohistochemistry in Triple-Negative Breast Cancer.

Background And Objective: Sacituzumab govitecan, an anti-trophoblast cell surface antigen 2 (TROP2) antibody-drug conjugate, has been approved by both the US Food and Drug Administration and European Medicines Agency for patients with metastatic triple-negative breast cancer who have received two or more prior systemic therapies, including at least one of them for advanced disease. Although TROP2 evaluation is not required for patient selection, survival data from the ASCENT trial show improved response rates in patients with high TROP2 expression by immunohistochemistry. However, there is no standardized testing assay for these patients.

Mucoepidermoid Carcinoma of the Breast: A Systematic Review of Clinicopathologic, Immunohistochemical, and Molecular Features.

Background: Mucoepidermoid carcinoma (MEC) of the breast is a very rare salivary gland-like tumor, accounting for 0.2%-0.3% of all breast cancers (BC).

Harmonization trial on testing strategies in ER+/HER2- breast cancer patients: an Italian experience.

Aims: To date, activating mutations acts as key player to clinically stratify estrogen receptor (ER)+/HER2-advanced breast cancer (BC) patients eligible to novel new generation oral Selective Estrogen Receptor Degraders (SERD) relapsing after first line aromatase inhibitors. Liquid biopsy represents the most useful biological source to detect activating mutations in clinical setting, but the lack of standardized pre-analytical and analytical procedures drastically impacts on detection rate of mutations in diagnostic specimens. Here, we sought to harmonize technical procedures comparing technical performance of diagnostically available testing strategies on a series of three reference specimens (sample A, B, C) harboring p.

Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules.

Purpose: The identification of novel molecular biomarkers may assist in the characterization of indeterminate thyroid nodules, which pose significant diagnostic challenges. Here, we aimed to explore the potential of proteomic analyses to support biomarker discovery in challenging thyroid lesions.

Methods: Linear Discriminant Analysis (LDA) was applied to Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) data from 44 thyroid neoplasms to select the most impactful molecular features for the classification of different tumor histologies, as well as for the distinction between NRAS-mutant (mNRAS) and NRAS-wild-type (wtNRAS) tumors.

Survival outcomes and prognostic factors in surgically resected lung carcinoids: A 25-year retrospective analysis.

Background: Carcinoids are rare neuroendocrine lung cancers with a prognosis related to stage and grade. Radical and complete surgical resection is the only curative treatment. However, some prognostic factors influencing survival outcomes must be fully understood.

Biomarker testing implementation for molecularly targeted therapy in non-small cell lung cancer patients.

Background: Recent advancements in identifying druggable molecular drivers in lung adenocarcinoma (LUAD), have transformed treatment paradigms. In recent years, Next Generation Sequencing (NGS) has gained momentum as an essential tool for in-depth simultaneous analysis of multiple genes, thereby streamlining the diagnostic process in LUAD. Despite this, the implementation of NGS testing in both the US and Europe remains suboptimal.

Consensus document on preoperative diagnostic procedures in breast lesions.

Currently, percutaneous sampling via core needle or vacuum-assisted biopsy is the primary choice to guide the management of patients with clinical or screen-detected breast lesions. Preoperative biopsies allow physicians to get pathological diagnoses as well as key prognostic and predictive data about the nature of the investigated process. Namely, adequate biopsy sampling is crucial for assigning lesions to one diagnostic category (B1-B5).

Retroperitoneal lymph node dissection for testis cancer: a comparison between open and robot-assisted approach in oncological and surgical outcomes.

Introduction: Retroperitoneal lymph node dissection (RPLND) is an integral part of the multidisciplinary treatment of Testis cancer (TC). Up to now, only few studies compared traditional open RPLND (O-RPLND) with minimally invasive approach. We investigated surgical outcomes and complication rates of patient with TC treated with O-RPLND or robot assisted (RA-RPLND).

International society of liquid biopsy (ISLB) perspective on minimal requirements for ctDNA testing in solid tumors.

Circulating tumor DNA (ctDNA) testing has transformed precision oncology by enabling the non-invasive detection of actionable mutations. To facilitate broader clinical adoption and improve testing accuracy, standardized quality criteria must be clearly defined and universally implemented. The International Society of Liquid Biopsy (ISLB) established the Quality Control and Accreditation Committee to develop consensus-based minimal standards for ctDNA analysis in oncology.

Key decision factors in second-line therapy: Expert insights on HR+/HER2-metastatic breast cancer post-CDK4/6 inhibitor progression.

The progression of HR+/HER2- metastatic breast cancer after treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) poses significant therapeutic challenges. Endocrine therapy (ET) remains a cornerstone of subsequent treatment, but its effectiveness depends on a nuanced understanding of clinical and genomic factors that drive therapy selection. For example, the duration of response to prior CDK4/6i therapy strongly predicts sensitivity to subsequent ET.

ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy.

Mutations in ESR1 play a critical role in resistance to endocrine therapy (ET) in hormone receptor-positive (HR +)/HER2- metastatic breast cancer (MBC). Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. While most studies have utilized liquid biopsy (LB) for mutation detection, the role of formalin-fixed paraffin-embedded (FFPE) tissue biopsy in this context remains unclear.

Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment.

Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2-positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood.

Inflammation and cancer cell survival: TRAF2 as a key player.

TNF receptor-associated factor 2 (TRAF2) plays a crucial role in both physiological and pathological processes. It takes part in the regulation of cell survival and death, tissue regeneration, development, endoplasmic reticulum stress response, autophagy, homeostasis of the epithelial barrier and regulation of adaptive and innate immunity. Initially identified for its interaction with TNF receptor 2 (TNFR2), TRAF2 contains a TRAF domain that enables homo- and hetero-oligomerization, allowing it to interact with multiple receptors and signaling molecules.

HER2-low across solid tumours: different incidences and definitions.

Antibody-drug conjugates, particularly trastuzumab deruxtecan (T-DXd), have emerged as effective therapies for various solid tumours. Clinical trials show that T-DXd improves survival in both HER2-positive and HER2-low breast cancer patients. Additionally, it improves survival in HER2-positive gastro-oesophageal cancer and elicits objective responses in HER2-low tumours.

Quantitative Proteomics and Phosphoproteomics Analysis of Patient-Derived Ovarian Cancer Stem Cells.

High-grade serous ovarian carcinoma (HGSOC) is the deadliest gynecologic cancer. Key to the progression and ultimate lethality of this subtype is the intra-tumoral heterogeneity, which is defined as the coexistence of different cell types and populations within a single tumor. Among those, ovarian cancer stem cells (OCSCs) are a distinct subpopulation of tumor cells endowed with stem-like properties, which can survive current standard therapies, resulting in tumor recurrence.

Compartmental surgery for squamous cell carcinoma of the buccal mucosa: description of a new surgical technique.

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer globally. Patient survival varies depending on tumour stage and oral cavity subsites. Buccal mucosa neoplasia is rare and burdened by worse prognosis than other oral subsites, showing a high rate of loco-regional relapses within six months after treatment.

Implementing digital pathology: qualitative and financial insights from eight leading European laboratories.

Digital Pathology (DP) revolutionizes the diagnostic workflow. Digitized scanned slides enhance operational efficiency by facilitating remote access, slide storage, reporting and automated AI image analysis, and enabling collaboration and research. However, substantial upfront and maintenance costs remain significant barriers to adoption.

ADT with SBRT versus SBRT alone for hormone-sensitive oligorecurrent prostate cancer (RADIOSA): a randomised, open-label, phase 2 clinical trial.

Background: Metastasis-directed therapy by stereotactic body radiotherapy (SBRT) has been shown to improve clinical outcomes in the oligometastatic prostate cancer setting. We aimed to investigate whether short-course androgen deprivation therapy (ADT) and SBRT at all oligometastatic sites versus SBRT alone improves clinical progression-free survival in men with metachronous oligorecurrent hormone-sensitive prostate cancer.

Methods: The RADIOSA study was a single-centre, randomised, open-label, controlled phase 2 trial done in the European Institute of Oncology, IRCCS, Milan, Italy.

Multimodal histopathologic models stratify hormone receptor-positive early breast cancer.

The Oncotype DX® Recurrence Score (RS) is an assay for hormone receptor-positive early breast cancer with extensively validated predictive and prognostic value. However, its cost and lag time have limited global adoption, and previous attempts to estimate it using clinicopathologic variables have had limited success. To address this, we assembled 6172 cases across three institutions and developed Orpheus, a multimodal deep learning tool to infer the RS from H&E whole-slide images.

The Regulatory Landscape of Biobanks In Europe: From Accreditation to Intellectual Property.

Biobanks are necessary resources for the storage and management of human biological materials, such as biofluids, tissues, cells, or nucleotides. They play a significant role in the development of new treatments and the advancement of basic and translational research, especially in the field of biomarkers discovery and validation. The regulatory landscape for biobanks, which is necessary to safeguard both privacy and scientific discoveries, exhibits significant heterogeneity across different countries and regions.

Next-generation sequencing for PTEN testing in HR+/HER2- metastatic breast cancer.

Molecular alterations in the Phosphoinositide 3-kinase (PI3K) pathway are key drivers of tumorigenesis and progression in hormone receptor-positive, HER2-negative (HR+/HER2 -) metastatic breast cancer (MBC). These genomic changes are actionable through targeted therapeutic agents. In particular, access to these therapies depends on accurate molecular testing of PIK3CA, AKT1, and PTEN.

Mismatch repair (MMR) and microsatellite instability (MSI) phenotypes across solid tumors: A comprehensive cBioPortal study on prevalence and prognostic impact.

Mismatch repair deficiency (MMR-d) and microsatellite instability (MSI) are prognostic and predictive biomarkers in oncology. Current testing for MMR/MSI relies on immunohistochemistry (IHC) for MMR proteins and molecular assays for MSI detection. This combined diagnostic strategy, however, lacks tumor specificity and does not account for gene variants.

Role of the International Society of Liquid Biopsy (ISLB) in establishing quality control frameworks for clinical integration.

Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, its wide adoption is hindered by a lack of standardized protocols, requiring robust quality control frameworks and harmonized diagnostic workflows. Large consensensus initiatives are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) testing, tailored to different disease types and stages.

The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit.

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials.