Carcinosarcomas are high-grade endometrial cancers which enclose mesenchymal and epithelial differentiated components. The vast majority of these cancers belong to the p53 abnormal molecular subgroup and usually come with an unfavorable prognosis. POLE mutant carcinosarcomas are a rarity and only make up about 5% of this histologic subtype. Recent literature even suggests that this number is still an overestimation and the result of misclassification of undifferentiated or dedifferentiated endometrial cancers. Here we present a case of a 56-years old patient diagnosed with carcinosarcoma of the uterus. Hysterectomy, bilateral salpingo-oophorectomy with pelvic lymph node staging was performed and complete molecular workup of the tumor revealed an abnormal p53 expression as well as a pathologic POLE mutation. NGS was performed separately on the epithelial and mesenchymal component of this high-grade cancer and both components shared two identical POLE mutations, a known pathologic mutation, and a variant of unknown significance (VUS). This finding hints to a clonal origin of both histologic components of this tumor and supports conversion theory as mechanism of carcinosarcoma emergence. The cancer was correctly staged as FIGO 2023 Stage IAmPOLEmut and according to ESGO-ESTRO-ESP guidelines adjuvant chemotherapy no longer considered and our patient entered follow-up after a detailed discussion.

OBJECTIVE: Molecular classification of endometrial cancer (EC) has become a promising information to tailor preoperatively the surgical treatment. We aimed to evaluate the rate of lymph node metastases (LNM) in patients with EC according to molecular profile.
METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines by searching in two major electronic databases (PubMed and Scopus), including original articles reporting lymph node metastases according to the molecular classification of EC as categorized in the ESGO-ESMO-ESP guidelines.
RESULTS: Fifteen studies enrolling 3056 patients were included. Pooled prevalence LNM when considering only patients undergoing lymph node assessment was 4% for POLE-mutated (95%CI: 0-12%), 22% for no specific molecular profile (95% CI: 9-39%), 23% for Mismatch repair-deficiency (95%CI: 10-40%) and 31% for p53-abnormal (95%CI: 24-39%).
CONCLUSIONS: The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.

Endometrial cancer is a common female gynecological neoplasia and its incidence rate has increased in the past years. Due to its predominant symptoms, most women will present uterine bleeding. It is usually diagnosed at an early stage and surgery has an important role in the treatment plan. The prognosis and quality of life of these patients can be quite favorable, if proper treatment is offered by surgeons. Traditionally, more invasive approaches and procedures were offered to these patients, but recent data suggest that more conservative and minimal invasive choices can be adopted in the treatment algorithm. Minimal invasive surgery, such as laparoscopy and robotic surgery, should be considered as an acceptable alternative, compared to laparotomy with less comorbidities and similar oncological and survival outcomes. Furthermore, sentinel lymph node biopsy has emerged in the surgical staging of endometrial cancer, in order to replace comprehensive lymphadenectomy. It is associated with less intra- and postoperative complications, while preliminary data show no difference in survival rates. However, sentinel lymph node biopsy should be offered within a strict algorithm, to avoid residual metastatic disease. The aim of this review is to analyze all the available data for the application of minimal invasive surgery in early endometrial cancer and especially the role of sentinel lymph node biopsy.

BACKGROUND: Gastric epithelial tumors exhibit morphological heterogeneity, diverse biological behaviors, and different oncopathological pathways. The Cancer Genome Atlas (TCGA) proposed a molecular classification of gastric adenocarcinomas based on genetic and molecular findings, which shows particular characteristics of diagnosis, prognosis, and indirectly, therapeutic alternatives. Within this classification, Epstein-Barr virus-positive (EBV+) and high microsatellite instability (MSI-H) subtypes stand out as subtypes that present a less aggressive biological behavior and a highly mutilated phenotype. This study conducted a systematic review with an emphasis on epidemiological and prognostic factors based on the molecular classification proposed by TCGA.
METHODS: A broad, comprehensive, and reproducible search with methodological rigor was conducted for study selection using the ROBINS-I and GRADEpro protocols and appropriate combinations of keywords.
RESULTS: A total of 25 studies were selected: six with a complete classification similar to TCGA and 19 with a distinction between MSI-H and EBV+. The application of meta-analysis calculations reinforces the prevalence of positive Epstein-Barr adenocarcinomas in males and high microsatellite instability in females, with a high level of certainty of evidence and low risk of bias in the analyzed studies due to the rigorous methods used.
CONCLUSIONS: The molecular classification proposed by TCGA shows limited dissemination, with MSI-H and EBV+ subtypes being the most researched, probably due to the benefit of the association with immunotherapies. However, the subclassification cannot be restricted to less than a quarter of the cases, and improvements in this aspect are urgent for the construction of knowledge on this important topic of global health.

Gastric cancer (GC) remains a disease with poor prognosis despite increasing availability of more effective targeted treatment. This may be in part due to the difficulty in selecting patients for appropriate treatment. Conventional taxonomic classifications of GC are ill-suited to make full use of recent advances in personalised therapy. In the past decade a number of molecular classifications have been proposed to address this; however, to date, there has been little implementation in the diagnostic routine. The lack of harmonisation between these classifications, the complexity and unavailability of some of the tests required plus the demands on time and resources, all contribute to poor uptake in the diagnostic routine. In the present study, these classifications were reviewed and an inclusive working classification that includes their main points, focuses on prognosis and treatment options and can be delivered using four on-slide tests (in situ hybridization for Epstein-Barr encoding region and immunohistochemistry for mismatch repair, E-cadherin and p53) is proposed. These tests can be performed on paraffin-embedded tissue and could be available in the majority of histopathology laboratories. The proposed classification also includes reflex testing for specific biomarkers relevant to treatment selection.

Background and objectives: This study aims to elucidate the prognostic implications of Epstein-Barr virus (EBV) infection in gastric carcinomas (GCs) through a systematic review and meta-analysis. Materials and Methods: In total, 57 eligible studies and 22,943 patients were included in this meta-analysis. We compared the prognoses of EBV-infected and non-infected GC patients. The subgroup analysis was performed based on the study location, molecular classification, and Lauren\'s classification. This study was checked according to the PRISMA 2020. The meta-analysis was performed using the Comprehensive Meta-Analysis software package. Results: EBV infection was found in 10.4% (95% confidence interval (CI) 0.082-0.131) of GC patients. The EBV-infected GC patients had a better overall survival compared with the EBV-non-infected GC patients (hazard ratio (HR) 0.890, 95% CI 0.816-0.970). In the subgroup analysis based on molecular classification, no significant differences were found between EBV+ and microsatellite instability and microsatellite stable (MSS)/EBV- subgroups (HR 1.099, 95% CI 0.885-1.364 and HR 0.954, 95% CI 0.872-1.044, respectively). In the diffuse type of Lauren\'s classification, EBV-infected GCs have a better prognosis compared with the EBV-non-infected GCs (HR 0.400, 95% CI 0.300-0.534). The prognostic impact of EBV infection was found in the Asian and American subgroups but not in the European subgroup (HR 0.880, 95% CI 0.782-0.991, HR 0.840, 95% CI 0.750-0.941, and HR 0.915, 95% CI 0.814-1.028). Conclusions: EBV infection is a favorable survival factor for GCs. However, the prognostic implications of EBV infection in the new molecular classification are not clear.

Breast cancer is the most common malignancy and the second most common cause of cancer-related mortality in women. Triple-negative breast cancers do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2 and have a higher recurrence rate, greater metastatic potential, and lower overall survival rate than those of other breast cancers. Treatment of triple-negative breast cancer is challenging; molecular-targeted therapies are largely ineffective and there is no standard treatment. In this review, we evaluate current attempts to classify triple-negative breast cancers based on their molecular features. We also describe promising treatment methods with different advantages and discuss genetic biomarkers and other prediction tools. Accurate molecular classification of triple-negative breast cancers is critical for patient risk categorization, treatment decisions, and surveillance. This review offers new ideas for more effective treatment of triple-negative breast cancer and identifies novel targets for drug development.

BACKGROUND: Molecular characterization plays a crucial role in glioma classification which impacts treatment strategy and patient outcome. Dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) perfusion imaging have been suggested as methods to help characterize glioma in a non-invasive fashion. This study set out to review and meta-analyze the evidence on the accuracy of DSC and/or DCE perfusion MRI in predicting IDH genotype and 1p/19q integrity status.
METHODS: After systematic literature search on Medline, EMBASE, Web of Science and the Cochrane Library, a qualitative meta-synthesis and quantitative meta-analysis were conducted. Meta-analysis was carried out on aggregated AUC data for different perfusion metrics.
RESULTS: Of 680 papers, twelve were included for the qualitative meta-synthesis, totaling 1384 patients. It was observed that CBV, ktrans, Ve and Vp values were, in general, significantly higher in IDH wildtype compared to IDH mutated glioma. Meta-analysis comprising of five papers (totaling 316 patients) showed that the AUC of CBV, ktrans, Ve and Vp were 0.85 (95%-CI 0.75-0.93), 0.81 (95%-CI 0.74-0.89), 0.84 (95%-CI 0.71-0.97) and 0.76 (95%-CI 0.61-0.90), respectively. No conclusive data on the prediction of 1p/19q integrity was available from these studies.
CONCLUSIONS: Future research should aim to predict 1p/19q integrity based on perfusion MRI data. Additionally, correlations with other clinically relevant outcomes should be further investigated, including patient stratification for treatment and overall survival.

The management of bladder cancer patients largely depends on pathologic staging and grading, and current morphological classification does not always show the individual patient\'s risk. Despite modern surgical techniques, pre- and postoperative therapies, clinical outcomes of these patients have not changed over decades. Today, there are new biomarkers for bladder cancer showing changes in tumor biology and progression, as a result of changes in the pathways affecting cell signaling, proliferation, apoptosis, epigenetic changes, angiogenesis, and modulation of host immune response. Assessment of multiple biomarkers associated with those pathways offers new understanding of tumor behavior while identifying important panels of predicting patient management and outcomes. In this review, the most important molecules and basics of the novel molecular classification of bladder cancer are presented.

The term \"ovarian carcinoma\" encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.