Emilio Peña-Ros

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in screening and therapeutic strategies, early detection and individualized treatment remain major challenges. In recent years, an expanding repertoire of biomarkers has emerged, spanning genomic, transcriptomic, proteomic, and metabolomic signatures. Epigenetic features, such as DNA methylation panels, as well as non-coding RNAs and the gut microbiome, hold potential not only for improving early diagnosis but also for refining prognosis and predicting therapeutic responses within the framework of precision oncology. This narrative review provides an updated, integrative overview of CRC diagnostic, prognostic, and predictive biomarkers. We distinguish established markers already in clinical practice, such as RAS and BRAF mutations, HER2 amplification, microsatellite instability/mismatch repair deficiency (MSI/dMMR), and widely investigated molecular alterations including TP53 mutations and immune-checkpoint-related markers, from novel biomarkers with growing translational potential. We also discuss the implementation challenges of these biomarkers in clinical practice, including issues related to validation, standardization, and cost-effectiveness, as well as the multi-modal approach for the development of composite diagnostic panels.

Adenoma-like adenocarcinoma (ALAC) of the colon is a recently recognized histological subtype of colorectal adenocarcinoma, characterized by a villous architecture, low-grade cytologic atypia, and deceptive bland morphology despite its invasive potential, which can mimic non-invasive adenomas, leading to underdiagnosis in limited biopsy samples. Herein, we report the case of an 81-year-old male presenting with right-upper-quadrant pain that was found to have a hepatic abscess and a 4 cm villous lesion in the ascending colon. Histopathological examination of the right hemicolectomy specimen revealed a villous adenocarcinoma with invasion of the muscularis propria, consistent with adenoma-like adenocarcinoma. Isolated loss of PMS2 indicated a mismatch repair deficiency. However, adjuvant therapy was not indicated. The patient remained recurrence-free for three years, until he died from unrelated causes in the context of progressive frailty and comorbidities, with no evidence of cancer progression. This case highlights the diagnostic challenges posed by ALAC and underscores the importance of recognizing its distinct morphological features. Awareness of this entity is essential to avoid misclassification and ensure adequate treatment, especially given its typically favorable prognosis with low metastatic potential.