Risk assessment in early colorectal cancer: histological and molecular markers

The pathological examination of early colorectal cancer specimens, in particular 'malignant polyps', provides important prognostic information. The depth of invasion into the submucosal layer assessed according to the Haggitt (for pedunculated lesions) or Kikuchi (for nonpolypoid lesions) classification systems or by direct measurement has been associated with the risk of lymph node metastasis. Angioinvasion, in particular lymphatic invasion, budding, tumor differentiation or grade, and resection margin status have been identified as further risk factors. The combination of these parameters allows the stratification of affected individuals into low- and high-risk categories, which is pivotal for clinical management. For low-risk cancers, defined as a completely excised Haggitt level 1-3/Kikuchi sm1 tumor with no evidence of poor differentiation or angioinvasion, local excision is generally regarded as adequate treatment. Oncological surgical resection is, however, indicated for high-risk cancers, which show at least one of the following features: Haggitt level 4/Kikuchi sm3 invasion, the presence of lymphatic (or vascular) invasion, poor differentiation, or positive resection margin. The inclusion of molecular markers such as tumor suppressor genes and their products, markers involved in tumor vascularization, and markers related to tumor cell adhesion and invasion may help to refine risk stratification, but data on molecular markers are still limited in this regard.