Risk Assessment in Early Colorectal Cancer: Histological and Molecular Markers

Abstract

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.

Multicentre prospective evaluation of real-time optical diagnosis of T1 colorectal cancer in large non-pedunculated colorectal polyps using narrow band imaging (the OPTICAL study)

“…Moreover, earlier studies reported that the risk of LNM is extremely low in deep invasive T1 CRC in the absence of other high-risk factors 29–32. Evolving molecular diagnostics have the potential to improve the prediction of LNM, and may expand the number of curative local minimal invasive resections 33. Furthermore, increased experience with en bloc endoscopic resection techniques such as ESD and full-thickness resection, and a better infrastructure to expert centres once cancer is suspected, might increase the number of en bloc resections with negative resection margins.…”

An evidence-based treatment algorithm for colorectal polyp cancers: results from the Scottish Screen-detected Polyp Cancer Study (SSPoCS)

“…An ideal predictive model would therefore identify those patients most likely to benefit from resection while preventing an excess of unnecessary operations. Previous studies have reported an array of ‘high-risk’ pathological features, including polyp size,20 location,21 lymphovascular invasion,12 poor differentiation,22 tumour budding,23 close or involved margins,12 23 sessile morphology24 and depth of submucosal invasion. The latter, in particular, is widely regarded as an important determinant of the likelihood of lymph node metastases and can be assessed in a number of different ways.…”

Newly recognized extratumoral features of colorectal cancer challenge the current tumor-node-metastasis staging system

“…The depth of infiltration by budding cells is currently shown to influence the frequency of lymph node metastases. Submucosal invasion <1000 μm (1 mm) is related with a low risk for nodal metastases [ 35 , 40 - 42 ], irrespective of the budding grade. However, the risk of nodal involvement in tumors invading beyond 1000 μm into submucosa (≥sm2), is related to the grade of TB, being exceptionally high in high-grade budding [ 44 ].…”