Endometrial cancer (EC) is one of the main causes of cancer-related death among women. In the last decade, the incidence of EC is on the rise, and the relative 5-year survival remains unchanged. This creates a dire need for new diagnostic and therapeutic approaches that can only result from a deeper understanding of the pathogenesis of the disease. In this direction, exosomes are under heavy research, with two main aims: to identify the potential diagnostic and prognostic markers and to develop technologies based on their use as therapeutic vectors targeting EC cells. Exosomes are widely available in all bodily fluids and are sources of ideal biomarkers for liquid biopsies. They are extracellular vesicles containing DNA, RNA, lipids, and proteins, which they transfer between cells, serving multiple functions and being implicated in both the physiological processes and the pathogenesis of diseases. Of all the biomolecules contained in exosomes, microRNAs (miRNAs) seem to have the most clinical utility in the diagnosis and treatment of EC. Exosomal miRNAs mediate the communication between EC cells, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and have a pivotal role in the tumor cells’ proliferation, epithelial to mesenchymal transition (EMT), and the formation of a tumor microenvironment. They participate in many processes that are tied to carcinogenesis and cancer progression, and they are therefore considered as attractive therapeutic targets. Here, we review the functions of exosomes in EC, focusing on potential biomarkers of diagnostic and prognostic significance or potential therapeutic use.

Background: The Paris System for Reporting Urinary Cytology (TPS) is considered the gold standard when it comes to diagnostic classifications of urine specimens. Its second edition brought some important changes, including the abolition of the diagnostic category of “low-grade urothelial neoplasm (LGUN)”, acknowledging the inability of cytology to reliably discern low-grade urothelial lesions. Methods: In this retrospective study, we assessed the validity of this change, studying the cytological diagnoses of histologically diagnosed low-grade urothelial carcinomas during a three-year period. Moreover, we correlated the sum of the urinary cytology diagnoses of this period with the histological diagnoses, whenever available. Results: Although all the cytological diagnoses of LGUN were concordant with the histological diagnoses, most low-grade urothelial carcinomas were misdiagnosed cytologically. Subsequently, the positive predictive value (PPV) of urinary cytology for the diagnosis of LGUN was 100%, while the sensitivity was only 21.7%. Following the cyto-histopathological correlation of the sum of the urinary cytology cases, the sensitivity of urinary cytology for the diagnosis of high-grade urothelial carcinoma (HGUC) was demonstrated to be 90.1%, the specificity 70.8%, the positive predictive value (PPV) 60.3%, the negative predictive value (NPV) 93.6% and the overall accuracy 77.2%, while for LGUN, the values were 21.7%, 97.2%, 87.5%, 58.6% and 61.9%, respectively. Risk of high-grade malignancy was 0% for the non-diagnostic (ND), 4.8% for the non-high-grade urothelial carcinoma (NHGUC), 33.3% for the atypical urothelial cells (AUCs), 65% for the suspicious for high-grade urothelial carcinoma (SHGUC), 100% for the HGUC and 12.5% for the LGUN diagnostic categories. Conclusions: This study validates the incorporation of the LGUN in the NHGUC diagnostic category in the second edition of TPS. Moreover, it proves the ability of urinary cytology to safely diagnose HGUC and stresses the pivotal role of its diagnosis.

Annexin A2 (ANXA2) is a protein that is involved in many physiological and pathological cellular processes. There is compelling evidence that its dysregulated expression, be it up- or downregulation, contributes to the oncogenesis of various neoplasms, including those of the digestive system. The present review summarizes the current knowledge on the role of ANXA2 in the main tumors of the digestive system. The clinical significance of ANXA2 is primordial, due to its potential use as a diagnostic and prognostic biomarker, and as a part of therapeutic protocols. Certain preclinical studies have shown that inhibiting ANXA2 or disrupting its interactions with key molecules can suppress tumor growth, invasion, and metastasis, as well as increase the cancer cells’ sensitivity to treatment in various cancers. Further research is needed to fully elucidate the complex role of ANXA2 in the carcinogenesis of tumors of the digestive system, and to translate these findings into clinical applications for improved diagnosis, prognosis, and treatment.

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target.

Objective: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. Methods: A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. Results: Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. Conclusions: This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters.

Esophageal cancer (EC) is a highly aggressive gastrointestinal malignancy, with a notable increase in incidence over recent decades, representing a significant global health burden. The main histological subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with the former being closely associated with gastroesophageal reflux disease, Barrett’s esophagus, and obesity, and its incidence continues to increase in Western populations. The rising incidence of EC, combined with poor survival rates, underscores the need for new therapeutic approaches. A deeper understanding of the molecular basis of this prevalent malignancy may open new avenues for optimal therapeutic strategies, with immunotherapy now central in several clinical trials. Understanding the interplay between the tumor microenvironment (TME) and disease progression is pivotal for managing this malignancy, which remains highly challenging. This review highlights the role of the TME in EAC progression and drug resistance, and recent therapeutic advances.