Background and Objectives: Early-onset colorectal cancer (EO-CRC) has become a significant public health concern due to its alarming rise in incidence and the poor prognosis associated with this disease. The aim of our study was to identify epidemiological, clinical, and paraclinical characteristics that could explain the more aggressive evolution of EO-CRC compared to late-onset colorectal cancer (LO-CRC). Materials and Methods: We conducted a retrospective study over a two-year period, including 204 patients diagnosed with colorectal cancer (CRC). The patients were divided into two subgroups: those with EO-CRC and those with LO-CRC. Statistical analysis was performed using IBM SPSS Statistics, Version 29.0. Results: EO-CRC was identified in 11.3% of the patients included in the study. Compared to LO-CRC patients, EO-CRC patients exhibited a tendency for more distal tumor localization and a stenotic endoscopic appearance (43.5% vs. 29.3%). Regarding histopathological diagnosis, EO-CRC patients demonstrated a higher proportion of the mucinous histologic subtype (34.8% vs. 14.4%) and a significantly greater percentage of poorly differentiated tumors (39.1% vs. 14.5%; p = 0.010). Immunohistochemical results, available for a limited number of patients, revealed higher CDX2 positivity in LO-CRC patients (p = 0.012) and higher HER2 positivity in EO-CRC patients (p = 0.002). Smoking (p = 0.006) and hypertension (p = 0.002) were more prevalent in EO-CRC patients than in LO-CRC patients. Conclusions: Patients with EO-CRC exhibit distinct histopathological and molecular characteristics compared to those with LO-CRC, which may contribute to their poorer prognoses. The higher prevalence of the mucinous histological subtype, poor tumor differentiation, increased HER2 expression, and reduced CDX2 expression suggest potential molecular pathways driving the aggressive nature of EO-CRC. These findings highlight the need for tailored screening strategies and personalized therapeutic approaches in younger CRC patients. Future studies should further investigate the underlying mechanisms and potential biomarkers that could guide early diagnoses and targeted treatments.

Background/Objectives: Mismatch repair (MMR) deficiency assessment has proven to be a valuable tool for prognostic evaluation and therapeutic management guidance in patients with colorectal cancer (CRC). Our study aimed to investigate the associations between MMR deficiency and a range of clinicopathological parameters. Methods: We conducted a retrospective observational study including 264 patients diagnosed with CRC, for whom immunohistochemical (IHC) data were available. Statistical analysis was performed using the Python 3.12.7 programming language within the Jupyter Notebook environment (Anaconda distribution). Results: MMR deficiency was identified in 18.18% of patients. It was significantly associated with younger age (<50 years), female sex, right-sided tumor location, poor tumor differentiation (G3), smoking, and loss of CDX2 expression (p < 0.001). MLH1 and PMS2 were the most frequently affected proteins, with concurrent loss in 77.08% of MMR-deficient cases. Loss of MLH1 expression correlated with female sex (p = 0.004), right-sided location (p < 0.001), poor differentiation (p < 0.001), and loss of CDX2 expression (p < 0.001). Additionally, the loss of PMS2 expression was associated with female sex (p = 0.015), right-sided tumor location (p = 0.003), and poor differentiation (p < 0.001). No significant associations were identified between MMR status and tumor stage, histological subtype, PLR, or NLR values. Conclusions: Gaining deeper insights into the clinical relevance of MMR status in CRC could contribute to improved testing rates and support the design of tailored management strategies that address the specific biological features of these tumors.

Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals, with a heterogeneous clinical spectrum spanning classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical forms. We synthesize contemporary epidemiology, immunopathogenesis, and the updated 2025 European Society for the Study of Coeliac Disease diagnostic framework. Adaptive responses to deamidated gliadin peptides presented by human leukocyte antigen (HLA)-DQ2/DQ8, together with interleukin-15-driven activation of intraepithelial lymphocytes (IELs), culminate in villous atrophy, crypt hyperplasia, and increased IELs. Serology centered on tissue transglutaminase immunoglobulin A (tTG-IgA) with total immunoglobulin A assessment remains first-line, complemented by standardized duodenal sampling (≥4 distal + 2 bulb biopsies) and selective HLA typing. The guidelines conditionally endorse a no-biopsy pathway for adults <45 years with tTG-IgA ≥10× upper limit of normal confirmed on a second sample, emphasizing shared decision-making and exclusion of red flags. We delineate differential diagnoses (tropical sprue, Crohn’s disease, common variable immunodeficiency, small intestinal bacterial overgrowth) and contrast CeD with non-celiac gluten sensitivity, which lacks villous atrophy, disease-specific serology, and HLA association. Emerging tools (immunohistochemistry, CD3/CD8/γδ IELs, video capsule endoscopy, confocal laser endomicroscopy) and the limitations of salivary/fecal assays are reviewed. Early detection improves quality of life and reduces healthcare utilization. Future directions include artificial intelligence-assisted imaging, molecular immunophenotyping, and non-dietary therapeutics.

Background: The mechanistic link between HERV-associated transcript expression and the inflammatory pathways involved in colorectal cancer (CRC), particularly the IL-17 axis, remains insufficiently characterized. We performed an exploratory paired-tissue study to investigate whether HERV-associated transcript deregulation in CRC aligns with a distinct local inflammatory signature, potentially consistent with endogenous retroviral re-expression linked to local immune activation and viral mimicry-related processes within the tumor microenvironment. Methods: Matched colorectal tumor tissue (T) and histologically tumor-free adjacent tissue (N) were obtained from 21 treatment-naive CRC patients. Expression of selected HERV-associated loci/transcripts (HERV-FRD, HERV-R, HERV-K, HERV-V1, HERV-1, HERV-H, and ERVWE1), HHLA1/HHLA2, IL-17 family members, and NFKB1 was assessed by RT–qPCR. Results: CRC tumors exhibited selective upregulation of HERV-FRD, HERV-R, HERV-K, HERV-V1, ERVWE1, HHLA1, and HHLA2, whereas HERV-1 and HERV-H showed no significant paired differences. IL-17E was also increased in tumor tissue, while NFKB1 did not show significant paired variation. Paired differential expression analysis [Δ(T−N)] identified a coordinated HERV/ERVWE1 signature that positively correlated with IL-17E after FDR correction, whereas HHLA1/HHLA2 displayed partially distinct behavior. No consistent associations were observed with clinicopathological variables. Conclusions: CRC appears to harbor a selective HERV/ERVWE1-associated transcriptional program linked to IL-17E, supporting a candidate inflammatory axis that may reflect a biologically relevant component of the tumor microenvironment. This expression pattern may also be compatible with a localized endogenous retroviral reactivation state linked to viral mimicry-related inflammatory signaling, although this interpretation remains indirect and requires mechanistic validation. These findings are associative and hypothesis-generating, but they provide a conceptual basis for future mechanistic validation and for exploring whether HERV-linked inflammatory signatures may have biomarker or therapeutic relevance in CRC.