Integrate studies on germline variations (GV) in patients with oral squamous cell carcinoma (OSCC), aiming to assess the highest frequencies of which genes were altered in patients with this diagnosis.

Accurate breast cancer risk prediction is essential for early detection and personalized prevention strategies. While traditional models, such as Gail and Tyrer-Cuzick, are widely utilized, machine learning-based approaches may offer enhanced predictive performance. This systematic review and meta-analysis compare the accuracy of traditional statistical models and machine learning models in breast cancer risk prediction.

Germline BRCA1/2 pathogenic variant carriers have an increased risk for high-grade serous carcinoma (HGSC) and are therefore advised to have risk-reducing salpingo-oophorectomy around the age of 40. However, a risk of 0.9% to develop peritoneal HGSC remains in these women, which increases to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected. The pathophysiological mechanism that leads to the development of peritoneal HGSC after salpingectomy or salpingo-oophorectomy is still largely unknown. In this systematic review, we aim to provide insights into the pathogenic pathways of peritoneal HGSC after salpingectomy or salpingo-oophorectomy. Therefore, we performed a systematic search for studies investigating pathophysiological mechanisms related to peritoneal HGSC in PubMed and EMBASE. A total of 49 articles were included in this study. Most evidence was found on mechanisms following a tubal origin, such as clonality between STIC and peritoneal HGSC as well as molecular similarities between fallopian tube (FT) epithelium and peritoneal HGSC. Additionally, FT epithelium was shown to adhere to the ovary and could therefore stay present after isolated salpingectomy. There might be a role for the endometrium, as it was observed that serous endometrial intraepithelial carcinoma (SEIC) has a clonal relationship with extra-uterine HGSC. The role of the ovary seems limited, although some mouse models show a role for follicular fluid in the dissemination of malignant cells on the peritoneum. In conclusion, different mechanisms might be responsible for peritoneal HGSC development after bilateral salpingectomy or salpingo-oophorectomy. Most available evidence supports the dissemination of precursor cells originating in the FT. Also, a possible role for the endometrium was found. An ovarian origin seems less likely; however, execution of oophorectomy does not seem obsolete in clinical practice as follicular fluid might promote dissemination and residual tubal tissue can be present on the ovary after salpingectomy.

With the widespread application of machine learning (ML) in the diagnosis and treatment of colorectal cancer (CRC), some studies have investigated the use of ML techniques for the diagnosis of KRAS (Kirsten rat sarcoma) mutation. Nevertheless, there is scarce evidence from evidence-based medicine to substantiate its efficacy.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fluctuating muscle weakness. MicroRNAs (miRNAs) have emerged as potential biomarkers for MG diagnosis, offering noninvasive and reliable detection. This systematic review and meta-analysis evaluated the diagnostic accuracy of miRNAs in MG. A comprehensive search of PubMed, Embase, and Google Scholar was conducted up to March 9, 2025. Eligible studies assessing miRNAs as MG biomarkers were selected on the basis of predefined criteria. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated via random effects model. Heterogeneity was assessed via I2, and publication bias was evaluated via Deeks' funnel plot. Nine studies including 1,797 participants were analysed. The pooled sensitivity and specificity were 0.80 (95% CI: 0.75-0.84) and 0.71 (95% CI: 0.65-0.77), respectively, with an area under the curve (AUC) of 0.83. Bivariate heterogeneity analysis indicated moderate variability, the cause of which were identified using subgroup analysis with region, clinical subtypes and seropositivity as subgroups. miRNAs demonstrate strong diagnostic potential for MG, with good sensitivity and specificity. However, standardized methodologies and further validation in large, multicentre studies is warranted.

HER2-positive breast cancer accounts for 15-20% of all breast cancers and is characterised by HER2 (also known as ERBB2) amplification. Although HER2-targeted therapies have markedly improved outcomes, current clinical-pathological variables and pathological complete response after neoadjuvant therapy are insufficient to fully capture biological heterogeneity and guide personalised treatment. HER2DX is a genomic test that integrates tumour biology and clinical data to stratify risk. Here, we conducted an individual patient-level meta-analysis to evaluate the association between the HER2DX risk score and survival outcomes in early-stage HER2-positive breast cancer.

Breast cancer presents with distinct clinical and molecular characteristics in the Middle East and North Africa (MENA) region, where women are diagnosed at younger ages and with more aggressive disease compared to Western populations. Despite the global burden, genomic studies of breast cancer in MENA remain underrepresented. This systematic review provides the first comprehensive analysis of somatic mutations in breast cancer patients across the MENA region.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the digestive tract, most commonly originating in the stomach or small intestine, and driven by activating mutations in the KIT or PDGFRA genes. Liquid biopsy has emerged as a promising, minimally invasive technique to detect and monitor circulating tumor DNA (ctDNA), offering real-time insights into tumor dynamics and treatment response. Specifically, detecting KIT/PDGFRA mutations in ctDNA may aid in assessing prognosis, therapeutic response, and resistance. However, the clinical utility of this approach remains unclear. To address this, we conducted a systematic review and meta-analysis to evaluate the prognostic relevance of ctDNA mutations in GIST patients by comparing survival outcomes between those with KIT/PDGFRA mutations and those with wild-type profiles or no detectable ctDNA.

The authors summarize the somatic mutational landscape of endometrial mucinous carcinoma of the gastric (gastrointestinal) type [MCG], based on findings from a 5-case cohort and a systematic review of the literature, the latter including 25 cases from 3 published reports. The 30 cases were analyzed by variably-sized next generation sequencing gene panels, and featured 74 total mutations, including 20 unique mutations [mean 2.47 ± 1.14 mutations/case; median= 2; range 1-5]. Mutations that were identified in > 1 case included TP53 (20/30, 66.7 %), KRAS (11/30, 36.7 %), PIK3CA (9/30, 30 %), BRCA2 (4/30, 13.3 %), STK11 (4/30, 13.3 %), ERBB2 (3/30, 10 %), SMAD4 (3/30, 10 %), FBXW7 (3/30, 10 %), ATM (3/30, 10 %), PTEN (2/30, 6.7 %), ARID1A (2/30, 6.7 %), and CDKN2A (2/30, 6.7 %). The most commonly reported combination of mutations [irrespective of the concurrent presence of other mutations] included KRAS + TP53 (9/30, 30.0 %), PIK3CA + TP53 (4/30, 13.3 %), SMAD4 + TP53 (3/30, 10 %), STK11 + TP53 (3/30, 10 %). Regarding molecular classification, most cases (20/30, 66.7 %) were p53-abnormal, with smaller subsets being dMMR (10 %), of "no specific molecular profile" (6/30, 20 %), and POLE mutated (1/30, 3.3 %). In summary, MCG may display a spectrum of mutations of potential clinicopathologic significance. TP53, KRAS and PIK3CA are the most commonly mutated genes in MCG. The four molecular subclasses of endometrial carcinoma are represented in MCG, with p53-abnormal being predominant. Our findings highlight the molecular landscape of this rare and incompletely characterized entity.

Biliary adenofibroma (BAF) is currently classified as a benign intrahepatic biliary tumor. However, a growing body of literature has documented BAFs with invasive components or associated cholangiocarcinoma. To better characterize this challenging entity, we performed a systematic review of BAF. PubMed, SCOPUS, and Embase were searched through April 2025 to identify all studies on BAFs. Clinicopathological, immunohistochemical (IHC), and molecular data have been extracted and analyzed. A total of 55 cases of BAF were identified in the literature. Macroscopically, BAFs usually showed mixed features, ranging from cysts intermingled with solid nodules to spongy, non-capsulated lesions. Histologically, the lining epithelium consisted of non-mucin-secreting biliary cells (55/55, 100 %). BAFs with invasive components accounted for 52.7 % of the literature (29/55). In two cases, innocent-looking tubulocystic structures were present but showed frankly invasive components. Although most patients were alive and disease-free after resection (35/43, 81.4 %), two patients died of disease (2/43, 4.6 %) and six experienced relapses (6/43, 14 %). In 7 studies with a total of 13 cases, molecular investigations demonstrated gene alterations typically seen in small-duct cholangiocarcinoma, including mutations in ARID1A (2/13), BAP1, PBRM1, and TP53 (one per case), and FGFR2 fusion (1/13). Taken together, our findings reveal that BAF is frequently associated with invasive malignancy. The frequent presence of tubulocystic structures with invasive features warrants further investigation of this entity, particularly given the challenging spectrum of the lesions in the differential diagnoses, ranging from benign to malignant neoplasms.

Histotype and grade of endometrial carcinoma (EC) have been cornerstones of risk assessment, as both are known to be associated with differences in prognosis. The aim of this study was to analyze the prognostic significance of grade and histotype (comparing low-grade endometrioid, high-grade endometrioid, serous, and all others) within each EC molecular subtype, with further stratification by stage. A cohort of 2478 patients with EC were identified from our center. Disease-specific survival was compared for tumors of each molecular subtype after stratification of patients into 1 of 4 groups (low-grade endometrioid, high-grade endometrioid, serous, other). In addition, a systematic review of the literature was undertaken to identify all previous studies where the prognostic significance of grade and histotype within molecular subtypes was reported. Grade and histotype were not of prognostic significance in POLE mut or p53abn EC across all stages and when just considering stage I ECs. MMRd low-grade ECs were associated with a better prognosis; however, they were also associated with lower stage disease, and within stage I tumors, grade and histotype were not of prognostic significance. Grade and histotype were of prognostic significance in NSMP ECs, in all stages and in the subset of stage I tumors ( P <0.001 for both analyses). On a systematic review of the literature, we identified 7 studies; there was no prognostic significance of grade and histotype (comparing low-grade endometrioid, high-grade endometrioid and serous) in POLE mut, and p53abn EC, and no prognostic significance of grade and histotype independent of stage in MMRd. Histotype and grade are strongly associated with prognosis in NSMP EC, but not in other molecular subtypes.

Gastric cancer is an aggressive and heterogeneous disease, primarily sporadic, with only 1-3% of cases being hereditary. However, gastric cancer is a component of several hereditary cancer syndromes. The BRCA1 and BRCA2 genes encode key DNA repair proteins involved in homologous recombination. Studies suggest a significantly increased risk of gastric cancer in first-degree relatives of BRCA1/2 mutation carriers.

Machine learning (ML) algorithms hold the potential to outperform the selection of patients for immunotherapy (ICIs) compared to previous biomarker studies. We analyzed the predictive performance of ML models and compared them to traditional clinical biomarkers (TCBs) in the field of gastrointestinal (GI) cancers. The study has been registered in PROSPERO (number: CRD42023465917). A systematic search of PubMed was conducted to identify studies applying different ML algorithms to GI cancer patients treated with ICIs using tumor RNA gene expression profiles. The outcomes included were response to immunotherapy (ITR) or survival. Additionally, we compared the ML methodology details and predictive power inherent in the published gene sets using 5-fold cross-validation and logistic regression (LR), on an available well-defined ICI-treated metastatic gastric cancer (GC) cohort (n = 45). A set of standard clinical ICI biomarkers (MLH, MSH, and CD8 genes, plus PMS2 and PD-L1)) and de-novo calculated principal components (PCs) of the original datasets were also included as additional points of comparison. Nine articles were identified as eligible to meet the inclusion criteria. Three were pan-cancer studies, five assessed GC, and one studied colorectal cancer (CRC). Classification and regression models were used to predict ICI efficacy. Next, using LR, we validated the predictive power of applied ML algorithms on RNA signatures, using their reported receiver operating characteristics (ROC) analysis area under the curve (AUC) values on a well-defined ICI-treated gastric cancer (GC) dataset (n = 45). In two cases our method has outperformed the published results (reported/LR comparison: 0.74/0.831, 0.67/0.735). Besides the published studies, we have included two benchmarks: a set of TCBs and using principal components based on the whole dataset (PCA, 99% explained variance, 40 components). Interestingly, a study using a selected gene set (immuno-oncology panel) with AUC = 0.83 was the only one that outperformed the TCB (AUC = 0.8) and the PCA (AUC =0.81) results. Cross-validation of the predictive performance of these genes on the same GC dataset and an investigation of their prognostic role on a collated multi-cohort GC dataset of n = 375 resected, or chemotherapy-treated patients revealed that genes mannose-6-phosphate receptor (M6PR), Indoleamine 2,3-Dioxygenase 1 (IDO1), Neuropilin-1 (NRP1), and MAGEA3 performed similarly, or better than established biomarkers like PD-L1 and MSI. We found an immuno-oncology panel with an AUC = 0.83 that outperformed the clinical benchmark or the PC results. We recommend further investigation and experimental validation in the case of M6PR, IDO1, NRP1, and MAGEA3 expressions based on their strong predictive power in GC ITR. Well-designed studies with larger sample sizes and nonlinear ML models might help improve biomarker selections.

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction, most commonly associated with autoantibodies against the acetylcholine receptor (AChR). While familial clustering of autoimmune MG (fMG) has been described, its prevalence and clinical characteristics remain uncertain. This study aimed to characterize autoimmune fMG cases in an Israeli cohort and describe global data through a systematic literature review.

Retinoblastoma is the most common intraocular malignancy in children. Although survival has improved with multimodal therapy, survivors remain at risk for subsequent malignant neoplasms (SMNs), often due to prior treatments or genetic predisposition. To identify risk factors associated with SMNs in childhood retinoblastoma survivors.

Treatment strategies for breast cancer have become increasingly complex over the years, requiring a deep understanding of disease pathology and the individualization of treatments on the basis of biomarkers. Circulating tumor DNA (ctDNA) enables non-invasive evaluation of the entire tumor, and its potential is being explored for treatment development. Numerous studies have evaluated ctDNA in various breast cancer subtypes during postoperative follow-up or after neoadjuvant chemotherapy, consistently showing that ctDNA positivity is associated with a higher risk of recurrence. Clinical trials evaluating therapeutic interventions on the basis of ctDNA status are also underway. Moving forward, the development of more sensitive assays and appropriate treatment strategies will be required. As the clinical application of ctDNA advances, the individualization of breast cancer treatment is expected to be further refined.

IntroductionThe MYCN oncogene promotes tumor cell proliferation in neuroblastoma, and its amplification is a well-established marker of poor prognosis. Radiomics-based approaches have shown promise in noninvasively determining MYCN amplification status; however, their diagnostic performance has varied significantly across studies. This systematic review and meta-analysis aimed to quantitatively evaluate the diagnostic accuracy of radiomics-based machine learning models for determining MYCN amplification in neuroblastoma and to critically assess the methodological quality of the included studies.MethodsA systematic search of articles published between January 1, 2000, and June 30, 2024, was conducted across PubMed, Embase, Web of Science, and the Cochrane Library. The articles focused on using radiomics to determine MYCN amplification in neuroblastoma. Methodological quality was assessed using the Radiomics Quality Score (RQS), METhodological RadiomICs Score (METRICS), and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools. A meta-analysis of validation performance was performed on studies with Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis statement Type 2a or higher.ResultsNine studies with 851 patients were included, and seven studies with 217 patients in the validation set were eligible for meta-analysis. The RQS scores ranged from 10 to 16 (mean 12), and METRICS scores ranged from 28.8% to 78.4% (mean 59.7%). QUADAS-2 assessment indicated that most studies had a low or unclear risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 0.78, 0.92, 9.45, and 0.24, respectively. The area under the summary receiver operating characteristic curve was 0.94 (95% confidence interval: 0.91-0.95).ConclusionDespite variability in study design and bias risk, radiomics shows promise as a non-invasive method for detecting MYCN amplification in neuroblastoma. Further refinement and validation in multicenter studies with larger sample sizes are needed to enhance its clinical applicability.

The effectiveness of PD-1 inhibitors for treating endometrial cancer (EC) remains a topic of debate. Guidelines lack consistency regarding the preferred treatments for advanced cases, as well as for patients experiencing metastasis or recurrence. Thus, our goal was to assess the efficacy of Dostarlimab, a PD-1 inhibitor, in EC by incorporating data from clinical trials to create a more comprehensive database.

Circulating tumour DNA (ctDNA) has become a noninvasive biomarker for dynamic monitoring of tumours. However, available evidence on postoperative ctDNA in patients with non-small cell lung cancer (NSCLC) is limited. This systematic review and meta-analysis aims to appraise the prognostic value of postoperative ctDNA in NSCLC.

Malignant pleural effusion (MPE) is a common complication of advanced malignancies, requiring differentiation from benign pleural effusion for appropriate management. Cytology and biopsy have limitations, necessitating more sensitive, less invasive diagnostic techniques. The objective of this study was to evaluate the diagnostic accuracy of methylated SHOX2 (short-stature homeobox 2) and RASSF1A (Ras association domain family member 1A) genes in detecting MPE.