The demand for bioactive secondary metabolites of natural origin is increasing every day. Micropropagation could be a strategy to respond more quickly to market demands, regardless of seasonality. This research aims to evaluate in vitro-grown plants of two hop varieties, namely Columbus and Magnum, as a potential source of bioactive compounds. The extracts were characterized in terms of total phenolic content by a Folin-Ciocalteu assay and antioxidant capacity by DPPH•, ABTS+, and FRAP assays. The bioactive compound profile of the extracts from both varieties was determined by using UPLC-ESI-QqQ-MS/MS. The results confirmed richness in (poly)phenols and other secondary metabolites of the in vitro-grown hop plantlets. Thirty-two compounds belonging to the major families of phytochemicals characteristic of the species were identified, and twenty-six were quantified, mainly flavonoids, including xanthohumol and isoxanthohumol, phenolic acids, as well as α- and β-acids. This study confirms the validity of in vitro-derived hop plantlets as source of bioactive compounds to be used in the nutraceutical, pharmaceutical, and food industries.

BACKGROUND: The active surveillance (AS) program for papillary thyroid carcinoma (≤ 1 cm) at low-risk (mPTC) showed a low percentage of progression.
OBJECTIVE: The aim of this study was to find a molecular signature of cases that showed disease progression during AS, which would allow their early identification.
METHODS: We performed next generation sequencing of 95 fine needle aspiration cytology specimens from cases prospectively enrolled in the AS program to analyze key somatic driver alterations or gene fusions implicated in PTC tumorigenesis. TERT promoter analysis was performed using Sanger sequencing or droplet digital PCR.
RESULTS: BRAF p.V600E was found in 66.3% (63/95) of mPTC and was the most common somatic alteration, followed by RAS oncogene mutations detected in 3.2% of mPTC (3/95: 2 NRAS and 1 KRAS) and gene fusions detected in 3.2% of mPTC (3/95: 1 RET-PTC1, 1 TFG-NTRK1, 1 ALK imbalance). No TERT promoter mutations (C228T and C250T) were found in the analyzed mPTC (84/95). The comparison between the molecular profile and the clinical outcome of the mPTC (stable versus progressive disease) showed no correlation (p-value=0.6) and did not identify a molecular signature able to identify progressive mPTC.
CONCLUSIONS: The molecular profile of mPTC is like that of bigger PTC with the exception that none of them showed a TERT promoter mutation. The identification of the most common driver mutations, such as BRAF, RAS, or gene fusions, is not helpful for the early identification of mPTC that will show disease progression during follow-up in the AS program.

BACKGROUND: Gastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN.
METHODS: The aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis.
RESULTS: Two patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13-4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel.
CONCLUSIONS: The current molecular profiles of IFN may help elucidate the mechanisms of IFN development.

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS-mutated and KRAS-wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes.

OBJECTIVE: Primary spinal cord glioblastoma (scGB) is a rare and aggressive spinal glioma, making up 7.5% of such cases. Whereas molecular profiles associated with improved overall survival (OS) are well studied for cranial glioblastoma (GB), the molecular characteristics of scGB are less documented. This review sought to document the molecular signatures of scGB, explore current treatment strategies, and evaluate clinical outcomes.
METHODS: A systematic literature review following the PRISMA guidelines searched the PubMed, Embase, and CENTRAL databases (January 1, 2013, to October 14, 2023) using glioblastoma-, spine-, and genetics-related keywords. Inclusion criteria were English-language articles on humans with histologically confirmed primary scGB, excluding drop metastases. Data on demographic characteristics, treatments, molecular profile, and outcome were extracted.
RESULTS: Over 10 years, 71 patients with adult primary scGB were reported in 31 papers. Most patients were located in Asia (53%) and the United States (23%). The median (range) age was 32 (24-47) years, with 61% of patients male. Tumors occurred primarily in the thoracic region (42%). Clinical presentation included motor deficits (92%), sensory deficits (86%), neck/back pain (68%), and bowel/bladder dysfunction (59%). Patients underwent subtotal resection (51%), gross-total resection (GTR) (23%), and biopsy (26%). Postoperative adjuvant treatment included concomitant external beam radiation therapy (XRT) and temozolomide (TMZ) in the majority of cases (66%), as well as palliative care without adjuvant treatment (17%). The molecular signature of scGB was similar to its cranial counterpart in terms of MGMT-promoter methylation (40% increased methylation) and higher for mutant TERT (50%) but decreased for wild-type tumor protein p53 (41% decreased mutation). Median (range) OS was 10 (6-18) months, and median progression-free survival (PFS) was 7 (3-10) months. PFS was significantly higher in patients treated with XRT/TMZ: median 15 months vs 4.5 months (95% CI -1.32 to 22.56, p < 0.05).
CONCLUSIONS: Primary scGB remains a rare disease with notable variations in treatment, potentially influenced by geographical availability. The observed molecular profile, when compared to that of cranial GB, emphasizes the need for further genomic validation and data collection. Surgical advancements to overcome the challenges of accomplishing GTR may contribute to improved OS.

Biliary tract cancers (BTCs) are rare and aggressive malignancies with an increasing incidence and poor prognosis. The standard systemic treatment for BTCs has evolved to include immune checkpoint inhibitors associated with gemcitabine-cisplatin as first-line therapies. However, survival rates remain low, highlighting the critical need for personalized treatment strategies based on molecular profiling. Currently, significant advancements have been made in the molecular characterization of BTCs, where genetic alterations, such as IDH1 mutations and FGFR2 fusions, provide targets for therapy. Molecular profiling is crucial early in the management process to identify potential candidates for clinical trials and guide treatment strategy. The integration of these molecular insights into clinical practice has allowed for the development of targeted therapies, although many of them are still in the phase 2 trial stage without definitive survival benefits demonstrated in phase 3 trials. This integration of comprehensive molecular profile insights with traditional treatment approaches offers a new horizon in the personalized medicine landscape for BTCs, with the aim of significantly improving patient outcomes through precision oncology.

OBJECTIVE: This study aims to investigate the impact of integrating molecular and histopathological findings into the revised International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system on patients initially diagnosed with stage I endometrial cancer (EC) according to the FIGO 2009 criteria.
METHODS: A cohort of 197 EC patients, initially classified as stage I under FIGO 2009, underwent restaging based on the updated FIGO 2023 criteria. The patients\' molecular and histopathological characteristics were documented, and their impact on upstaging was analyzed.
RESULTS: Molecular profiling was conducted for 81.2% (160/197) of the patients, revealing that 55.3% (109/197) were classified as non-specific molecular profile, 14.7% (29/197) as mismatch repair deficiency, 11.2% (22/197) as p53 abnormality (p53abn), and 18.8% (37/197) as unknown. Upstaging was identified in 26.9% (43/160) of the 160 patients with known molecular profiles. Among the upstaged patients, 51.2% experienced upstaging due to p53 abnormality, 20.9% due to substantial lymphovascular space invasion (LVSI), 20.9% due to aggressive histological types, and 6.9% due to high grade.
CONCLUSIONS: The introduction of the molecular profile into the revised FIGO 2023 staging system for stage I EC has led to notable changes in the staging of approximately one-fifth of patients. While p53 abnormalities have emerged as the most influential factor contributing to the upstaging, LVSI and aggressive histological types also represent significant contributing factors.

OBJECTIVE: To gather real-life data on biliary tract cancer (BTC) in France, an ambispective ACABi GERCOR Pronobil cohort was initiated. This nested study, Amber, utilized data from this cohort to document clinical practices in this setting.
METHODS: Inclusion criteria encompassed patients with locally advanced/metastatic BTC managed between 2019 and 2021 in nine French referral hospitals. Objectives included describing demographic and clinical data, treatments outcomes (safety and efficacy), and overall survival.
RESULTS: Of the 138 patients (median age 65 years, a balanced sex ratio) included, most displayed ECOG 0-1 (83 %), at least one comorbidity (79 %), and had intrahepatic (56 %) and metastatic (82 %) BTC. Among surgically-resected patients, 60 % received adjuvant chemotherapy, mainly capecitabine (67 %). CisGem, the primary first-line palliative chemotherapy (69 %), showed a 23 % objective response rate, a median progression-free survival of 5.3 months, and a median overall survival of 13.4 months. Second-, third-, and fourth-line were given to 75 % (FOLFOX: 35 %, targeted therapy: 14 %), 32 %, and 13 % of patients. In total, 67 % of patients had a molecular profile (IDH1 mutations and FGFR2 fusions: accounting for 21 % each in intrahepatic cholangiocarcinoma).
CONCLUSIONS: BTC patients were predominantly treated according to international recommendations. The obtained demographic, tumor, and molecular data were consistent with existing literature.

BACKGROUND: Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS.
METHODS: The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry. A panel of 46 ancestry-informative markers determined patients\' genetic ancestry.
RESULTS: The most frequently mutated gene was EGFR (49.6%), followed by TP53 (39.5%), ALK (12.6%), ERBB2 (7.6%), KRAS (5.9%), PIK3CA (1.7%), and less than 1% alterations in RET, NTRK1, MET∆ex14, PDGFRA, and BRAF. Except for TP53 and PIK3CA, all other alterations were mutually exclusive. Genetic ancestry analysis revealed a predominance of European (71.1%), and a higher African ancestry was associated with TP53 mutations.
CONCLUSIONS: Brazilian LCINS exhibited a similar molecular profile to other populations, except the increased ALK and TP53 alterations. Importantly, 73% of these patients have actionable alterations that are suitable for targeted treatments.

BACKGROUND: Spindle cell lipomas (SL) and pleomorphic lipomas (PL) are rare variants of lipomas, occurring predominantly in the head and neck region. Laryngeal SL/PL is very uncommon and causes obstructive symptoms needing immediate intervention. These tumors are often challenging in radiology due to the admixture of elements and the presence of adipose tissue may help in diagnosis. From a surgeon\'s perspective, understanding the nuances of SL/PL is paramount. Histology is the gold standard for diagnosis; however, it often causes diagnostic challenges in biopsy.  Method: A retrospective review of the clinical and pathologic features of archival cases of SL/PL was performed.
RESULTS: A total of six cases of head and neck region SL/PL were identified. The age of patients ranged from 21 to 58 years and the male-to-female ratio was 5:1. The tumors were distributed in the nape of the neck (n=3), laryngeal region (n=2), and orbit (n=1). Histology in all the cases showed a low-grade neoplasm composed of a variable amount of spindle cells and adipose tissue. The stroma was myxoid in most cases. CD34 was diffusely positive in all the cases.
CONCLUSIONS: SLs are a rare and uncommon variant of lipoma with a predilection in the head and neck region. They are low-grade neoplasms with a propensity to recur after years. Having knowledge of this tumor can improve surgical outcomes and better patient care.