[Colorectal carcinogenesis: a historical review]

Area of Science:

• Gastroenterology
• Oncology
• Molecular Biology

Context:

• The concept of colorectal carcinogenesis has evolved significantly over the past two decades.
• Historical perspectives trace the understanding from surgical materials to molecular biology insights.
• The traditional adenoma-carcinoma sequence has been refined by new discoveries.

Purpose:

• To provide a historical review of the changing concepts in colorectal carcinogenesis.
• To delineate the evolution of understanding through four distinct periods.
• To highlight the shift in focus towards nonpolypoid neoplasms and molecular pathways.

Summary:

• Early concepts focused on large adenomas as precursors (adenoma-carcinoma sequence).
• Subsequent research identified smaller, non-pedunculated adenomas and nonpolypoid neoplasms (flat, depressed) as significant precursors with higher malignant potential.
• Molecular biology has revealed distinct genetic pathways, such as the absence of K-ras mutations in nonpolypoid lesions, suggesting novel carcinogenesis mechanisms and the concept of de novo carcinoma.

Impact:

• This review reframes the understanding of colorectal cancer origins.
• It emphasizes the importance of recognizing diverse precursor lesions and their distinct molecular characteristics.
• The findings contribute to more accurate risk assessment and targeted prevention strategies for colorectal cancer.