Homologous recombination deficiency in ovarian cancer: Global expert consensus on testing and a comparison of companion diagnostics.

Background: Poly (ADP ribose) polymerase inhibitors (PARPis) are a treatment option for patients with advanced high-grade serous or endometrioid ovarian carcinoma (OC). Recent guidelines have clarified how homologous recombination deficiency (HRD) may influence treatment decision-making in this setting. As a result, numerous companion diagnostic assays (CDx) have been developed to identify HRD.

The role of the pathologist in the design and conducting of biomarker-driven clinical trials in cancer: position paper of the European Society of Pathology.

Clinical trials in oncology are important tools to identify and establish new effective drugs for cancer treatment. Since the development of the concept of precision oncology, a huge number of multi-centric biomarker-driven clinical trials have been performed and promoted by either academic institutions or pharmaceutical companies. In this scenario, the role of pathologists is essential in multiple aspects, with new challenges that should be addressed.

FIGO 2023 staging for endometrial cancer, when, if it is not now?

Incorporation of pathological and (not mandatory) molecular features into the new FIGO 2023 staging system has generated some controversy. Several validations have been published recently that demonstrated the higher prognostic precision of FIGO 2023 compared to the previous FIGO 2009 scheme. In the present article, the authors want to respond to some concerns that were raised by some pathologists and clinicians.

Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer.

Objective: The prognostic relevance of hormonal biomarkers in endometrial cancer (EC) has been well-established. A refined three-tiered risk model for estrogen receptor (ER)/progesterone receptor (PR) expression was shown to improve prognostication. This has not been evaluated in relation to the molecular subgroups.

Tumor specimen cold ischemia time impacts molecular cancer drug target discovery.

Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter.

Role of cfDNA and ctDNA to improve the risk stratification and the disease follow-up in patients with endometrial cancer: towards the clinical application.

Background: There has been a rise in endometrial cancer (EC) incidence leading to increased mortality. To counter this trend, improving the stratification of post-surgery recurrence risk and anticipating disease relapse and treatment resistance is essential. Liquid biopsy analyses offer a promising tool for these clinical challenges, though the best strategy for applying them in EC must be defined.

Histologic and Molecular Type Changes in Endometrial Cancer Recurrences in Comparison With Their Corresponding Primary Tumors.

In this study, molecular alterations in endometrial carcinoma (EC) recurrences were analyzed. We aimed to identify genes implicated in tumor progression and to evaluate whether histologic and molecular type shifting occurs in recurrences. Thus, we analyzed 50 samples corresponding to 24 primary ECs (15 low-grade endometrioid endometrial carcinomas [LG-EECs] and 9 high-grade endometrial carcinomas) and their corresponding 26 recurrences.

Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors.

Extracellular adenosine triphosphate (ATP) conducts a complex dynamic system of broadly represented cell signaling. Ectonucleotidases are the enzymes with nucleotide hydrolytic ability that regulate ATP levels in physiological and pathological conditions, thus playing a key role in the so-called purinergic signaling. Altered ectonucleotidase expression has been reported in cancer, and the ectonucleoside triphosphate diphosphohydrolase (NTPDase) family of enzymes, with its best-known form NTPDase1 (CD39), is targeted in cancer immunotherapy.

Metabolic Dysfunction-Associated Steatotic Liver Disease in Severe Obesity and Concordance between Invasive (Biopsy) and Noninvasive (OWLiver®) Diagnoses.

Introduction: Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods.

Methods: A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy.

Influence of nonalcoholic fatty liver disease severity on carotid adventitial vasa vasorum.

Introduction: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the world's population and encompasses a spectrum of liver conditions, from non-alcoholic steatohepatitis (NASH) to inflammation and fibrosis. In addition, NAFLD also links to extrahepatic conditions like diabetes or obesity. However, it remains unclear if NAFLD independently correlates with the onset and progression of atherosclerosis.

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

Background: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear.

Biomarker characterization in endometrial cancer in Europe: first survey data analysis from 69 pathological academic and hospital labs.

Introduction: Endometrial carcinoma (EC) is the commonest gynecological cancer affecting women in Western populations. To predict patient risk, the 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract stressed the importance of integrated histo-molecular classification of the disease. This survey analysis poses attention on the most frequently used immunohistochemical and molecular markers adopted in daily categorization of ECs in European laboratories.

2023 FIGO staging system for endometrial cancer: The evolution of the revolution.

Embracing the complex and diverse nature of the heterogenous group of malignancies that are included under the umbrella of "endometrial cancer" (EC) to better align prognosis with treatment recommendations, requires a more comprehensive staging system. Our goal at the development of the new FIGO staging was to provide 1) high accuracy in the predictive prognosis for a patient with EC, which is the genuine purpose of a staging system, and 2) identification of distinct treatment relevant subgroups. Since the publication of the 2009 staging system by the International Federation of Gynecology and Obstetrics (FIGO) 14  years ago (1, 2), our understanding of the biology and natural history of EC has undergone a radical transformation.

ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer.

Molecular profiling and feasibility using a comprehensive hybrid capture panel on a consecutive series of non-small-cell lung cancer patients from a single centre.

Background: Targeted next-generation sequencing (NGS) is recommended to screen actionable genomic alterations (GAs) in patients with non-small-cell lung cancer (NSCLC). We determined the feasibility to detect actionable GAs using TruSight™ Oncology 500 (TSO500) in 200 consecutive patients with NSCLC.

Materials And Methods: DNA and RNA were sequenced on an Illumina® NextSeq 550 instrument and processed using the TSO500 Docker pipeline.

Ovarian cancer relies on the PDGFRβ-fibronectin axis for tumorsphere formation and metastatic spread.

High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites.

Metformin exhibits antineoplastic effects on Pten-deficient endometrial cancer by interfering with TGF-β and p38/ERK MAPK signalling.

Metformin is a widespread antidiabetic agent that is commonly used as a treatment against type 2 diabetes mellitus patients. Regarding its therapeutic potential, multiple studies have concluded that Metformin exhibits antineoplastic activity on several types of cancer, including endometrial carcinoma. Although Metformin's antineoplastic activity is well documented, its cellular and molecular anticancer mechanisms are still a matter of controversy because a plethora of anticancer mechanisms have been proposed for different cancer cell types.