The high morbidity and mortality of colorectal cancer (CRC) remain a worldwide challenge, despite the advances in prevention, diagnosis, and treatment. RAS alterations have a central role in the pathogenesis of CRC universally recognized both in the canonical mutation-based classification and in the recent transcriptase-based classification. About 40% of CRCs are KRAS mutated, 5% NRAS mutated, and only rare cases are HRAS mutated. Morphological and molecular correlations demonstrated the involvement of RAS in cellular plasticity, which is related to invasive and migration properties of neoplastic cells. RAS signalling has been involved in the initiation of epithelial to mesenchymal transition (EMT) in CRC leading to tumour spreading. Tumour budding is the morphological surrogate of EMT and features cellular plasticity. Tumour budding is clinically relevant for CRC patients in three different contexts: (i) in pT1 CRC the presence of tumour buds is associated with nodal metastasis, (ii) in stage II CRC identifies the cases with a prognosis similar to metastatic disease, and (iii) intratumoral budding could be useful in patient selection for neoadjuvant therapy. This review is focused on the current knowledge on RAS in CRC and its link with cellular plasticity and related clinic pathological features.

Thank you, and Regards,

John Robert
Journal of Medical and Surgical Pathology
ISSN: 2472-4971 | NLM ID: 101245791