Publications by authors named "Antonino Iaccarino"

Despite recent advances, biliary tract cancer (BTC) remains one of the most lethal tumor worldwide due to late diagnosis, limited therapeutic strategies and resistance to conventional therapies. In recent years, high-throughput technologies have enabled extensive genome, and transcriptome sequencing unveiling, among others, the regulatory potential of microRNAs (miRNAs). Compelling evidence shown that miRNA are attractive therapeutic targets and promising candidates as biomarkers for various therapy-resistant tumors.

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Introduction: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples.

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Neutrophil gelatinase-associated lipocalin (NGAL), a siderophore-mediated iron binding protein, is highly expressed in human anaplastic thyroid carcinomas (ATCs) where it plays pleiotropic protumorigenic roles including that of a prosurvival protein. Here we show that NGAL inhibits FAS/CD95 death receptor to control ATC cell survival. FAS/CD95 expression in human specimens from patients with ATC and in ATC-derived cell lines negatively correlate with NGAL expression.

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Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have been approved in combination with endocrine therapy (ET) to treat estrogen receptor-positive (ER+) metastatic breast cancer (BC). However, drug resistance represents the leading cause of breast cancer patients mortality. This study aimed to identify novel resistance mechanisms to ER antagonists in combination with CDK4/6 inhibitors.

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Aims: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised.

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Background: The management of cutaneous melanoma has changed dramatically in recent years thanks to the development of tyrosine kinase and immune-checkpoint inhibitors (ICIs). Thus, multiple biomarker testing is becoming ever more important for the identification of patients who are potentially eligible for these treatments. One reliable approach to the molecular evaluation of metastatic melanoma is fine needle cytology (FNC).

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Article Synopsis
  • - Fine needle cytology (FNC) is an effective first-line method for diagnosing lymph node metastases, helping to determine if a cancer is non-haematopoietic.
  • - The study analyzed 982 cytology cases over 10 years, dividing them into two groups: "oncological" (previous cancer history) and "naïve" (no relevant history), with 84.92% achieving a secondary diagnostic level. !* - Results showed that while less material was available for naïve cases, a high percentage (82.49%) still allowed for a second level diagnosis by integrating various clinical and morphological data. !*
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  • Immune-checkpoint inhibitors (ICIs) are improving treatment options for patients with advanced stage non-small cell lung cancer (NSCLC), but their effectiveness in oncogene-addicted cases is still under debate.
  • The study analyzed 167 PD-L1 positive NSCLC patients to explore the presence of genomic alterations in five driver oncogenes.
  • Findings revealed that over half of the patients had genomic alterations, and despite these alterations, 37.5% of patients with high PD-L1 expression showed clinical benefit from ICIs.
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, ,  and gene fusions and exon 14 skipping alterations represent novel predictive biomarkers for advanced non-small-cell lung cancer (NSCLC). Therefore, testing patients for these genetic variants is crucial for choosing the best selective treatment. Over the last couple of decades, next-generation sequencing (NGS) platforms have emerged as an extremely useful tool for detecting these variants.

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Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients.

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In the era of personalised medicine, testing for an increasing number of predictive biomarkers is becoming a priority. However, tissue biopsies from these patients are oftentimes insufficient for conventional approaches, a common issue that deprives them of the clinical benefits of biomarker-directed treatments. To tackle this problem, many clinical laboratories are resorting to circulating tumour DNA (ctDNA), which is becoming increasingly appreciated as a valuable source for biomarker testing.

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DNA mismatch repair complex is involved in the maintenance of DNA stability. In the recent years, a plethora of technical approaches for microsatellite instability (MSI) analysis emerged. Here, we review the results of our MSI status evaluation by adopting a customised workflow on microfluidic system obtained in 4 years of diagnostic routine practice.

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Background: Rearranged during transfection () gene fusions are detected in 10-20% of thyroid cancer patients. Recently, fusion-positive metastatic thyroid cancers have attracted much attention owing to the FDA approval of two highly selective anti-RET tyrosine kinase inhibitors, namely, selpercatinib, and pralsetinib.

Areas Covered: This review summarizes the available evidence on the biological and predictive role of gene fusions in thyroid carcinoma patients and the latest screening assays currently used to detect these genomic alterations in histological and cytological specimens.

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Objective: In this review, we evaluate the role of liquid biopsy in managing lung cancer patients during the still ongoing coronavirus disease 2019 (COVID-19) healthcare emergency.

Background: The novel influenza coronavirus (severe acute respiratory syndrome coronavirus or SARS-CoV-2) has upended several aspects of our lives, including medical activities. In this setting, many routine cancer diagnostic and therapeutic procedures have been suspended, leading to delays in diagnosis, treatments, and, ultimately, increases in cancer mortality rates.

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Article Synopsis
  • A global survey revealed a significant decrease in the number of cytological specimens processed during the post-lockdown period of 2020, compared to 2019, with a drop of 26.5%.
  • Despite fewer specimens, the malignancy rates increased notably, indicating potential unmet needs in cancer diagnosis during the pandemic.
  • The data suggests a gradual return to normalcy in cytopathology practices, as seen in the increased workload late in the post-lockdown phase.
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Tumor interstitial fluid (TIF) surrounds and perfuses tumors and collects ions, metabolites, proteins, and extracellular vesicles secreted by tumor and stromal cells. Specific metabolites, accumulated within the TIF, could induce metabolic alterations of immune cells and shape the tumor microenvironment. We deployed a metabolomic approach to analyze the composition of melanoma TIF and compared it to the plasma of C57BL6 mice, engrafted or not with B16-melanoma cells.

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Although gene fusions occur rarely in non-small-cell lung cancer (NSCLC) patients, they represent a relevant target in treatment decision algorithms. To date, immunohistochemistry and fluorescence hybridization are the two principal methods used in clinical trials. However, using these methods in routine clinical practice is often impractical and time consuming because they can only analyze single genes and the quantity of tissue material is often insufficient.

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Immune-checkpoint inhibitors (ICIs) play a key role in the treatment of advanced stage colorectal cancer (CRC) patients featuring a deficient DNA mismatch repair (dMMR) system or a high microsatellite instability (MSI-H) profile. However, beyond the established role in CRC patients, ICIs have highly proven efficacy in other solid tumors featuring MSI-H/dMMR status represented by endometrial, gastric, ovarian, prostatic, and pancreatic carcinomas (EC, GC, OC, PrC, and PaC). Our aim was to compare the concordance rates among the Idylla™ MSI test, TapeStation 4200, and immunohistochemical (IHC) analysis in assessing MSI-H/dMMR status in EC, GC, OC, PrC, and PaC patients.

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Aims: Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated.

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Article Synopsis
  • Immunotherapy has become a key treatment for cancer, focusing on the PD-1/PD-L1 pathway through the use of monoclonal antibodies in various cancer types.
  • Research is exploring the potential of testing PD-L1 on cytological samples rather than just tissue specimens, which shows promise but presents significant challenges.
  • The review highlights existing knowledge gaps in cytopathology related to immuno-oncology, emphasizing issues like sample preparation, correlation with histology, and consistency among different observers.
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Aims: In metastatic colorectal carcinomas (mCRC), / genes mutations are first tested to determine the eligibility for anti-EGFR (Epidermal Growth Factor Receptor) therapy in combination with conventional cytotoxic agents. Recent advancements in next-generation sequencing (NGS) have highlighted the potential of multi-gene panels. This multi-gene analysis may provide useful information for the molecular characterisation of mCRC, other than the status of genes.

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Aims: In thyroid cytopathology, the undetermined diagnostic categories still pose diagnostic challenges. Although next-generation sequencing (NGS) is a promising technique for the molecular testing of thyroid fine-needle aspiration (FNA) specimens, access to such technology can be difficult because of its prohibitive cost and lack of reimbursement in countries with universal health coverage. To overcome these issues, we developed and validated a novel custom NGS panel, specifically designed to target 264 clinically relevant mutations involved in thyroid tumourigenesis.

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Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) representing its most commonly diagnosed sub-type. Despite the significant improvements in lung cancer biomarkers knowledge, accompanied by substantial technological advances in molecular tumor profiling, a considerable fraction (up to 30 %) of advanced NSCLC patient presents with major testing challenges or tissue unavailability for molecular analysis. In this context, liquid biopsy is on the rise, currently gaining considerable interest within the molecular pathology and oncology community.

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Whenever tissue sample is not available, non-small cell lung cancer (NSCLC) biomarker testing is performed with liquid biopsy. The Kirsten rat sarcoma viral oncogene homolog () p.G12C mutation is a novel target in patients with NSCLC.

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