Inguinal orchiectomy is curative in 70–80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays. Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3–9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations. Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT.

Introduction: Ataxia-Telangiectasia Mutated (ATM) is a cancer predisposition gene; carriers of germline pathogenic variants have an increased risk of developing malignancies, including breast, prostate, pancreatic, and ovarian cancer. Most ATM variants are of uncertain significance. Findings from genome-wide association studies (GWAS) suggest that ATM may be a low-risk melanoma susceptibility locus. Case Report: We report the case of a Hispanic family whose members who have presented cutaneous melanoma have been found to be carriers for the ATM pathogenic variant c.3747-1G>C (rs730881364), one of whom was diagnosed at 24 years old. Discussion: We describe for the first time the possible clinical association between ATM (c.3747-1G>C) and familial melanoma. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site, assuming a variant that entails loss of functionality that is probably pathogenic and related to oncogenesis. However, we cannot exclude that cutaneous melanoma in both members and at an early age is the result of chance, environmental interaction, other uncontrolled external factors, or the interaction of other genetic alterations other than the ATM variant described in this study.

Colorectal cancer (CRC) remains a major global health burden and a leading cause of cancer-related morbidity and mortality. Current blood-based biomarkers lack sufficient sensitivity and specificity, particularly for early detection. In this context, circulating immune-cell transcriptomic profiling has emerged as a promising minimally invasive approach. This systematic review was conducted following a PROSPERO-registered protocol (CRD42024604757) and PRISMA 2020 guidelines to evaluate the diagnostic and prognostic potential of circulating monocyte-related transcriptomic profiles in CRC. Of 295 records identified, six studies met the inclusion criteria. The available evidence consistently supports the diagnostic value of circulating transcriptomic profiles in distinguishing patients with CRC from healthy individuals and in reflecting tumour-associated immune alterations. Monocyte-related signatures, including CXCR2⁺ monocytes, were associated with disease stage and metastatic features. Epitranscriptomic modifications, such as m6A and m5C, further reinforced their diagnostic relevance, with some studies reporting higher diagnostic accuracy than classical biomarkers. In contrast, evidence for prognostic value remains limited, heterogeneous, and often indirect, largely due to small sample sizes, methodological variability, and reliance on public datasets. Overall, circulating immune-cell transcriptomic profiles are promising non-invasive biomarkers for CRC detection and characterization, although their prognostic utility remains unclear. Methodological heterogeneity limits clinical applicability, highlighting the need for standardized, CRC-specific studies with cell-type-resolved approaches.