Endoscopy, Morphology, Morphometry and Molecular Markers: Predicting Cancer Risk in Colorectal Adenoma

Kjetil Søreide; Bjørn S Nedrebø; Andreas Reite; Kenneth Thorsen; Hartwig Kørner


Expert Rev Mol Diagn. 2009;9(2):125-137. 

In This Article

Abstract and Introduction


The evaluation of short- and long-term risk for developing cancer in patients with colorectal adenomas is controversial. Good, reliable predictors of cancer risk in any adenoma are currently lacking and are limited to adenoma size, number and histologic type. In fact, the evaluation of any adenoma or precancer lesion (e.g., hyperplastic polyps, serrated adenoma or aberrant crypt foci) within the colorectum may be assessed by a number of techniques ranging from direct visualization through the endoscope, to microscopic assessment, and to evaluation at the molecular level. Emerging techniques may yield improved methods of adenoma risk-assessment in the near future. For one, newer endoscopy technologies include chromoendoscopy or endocytoscopy, which now render endoscopists able to resolve the surface and subsurface mucosa at cellular resolution in vivo and in real time - thus, bringing the microscope to the patient's bedside. This new era in endoscopic imaging is dubbed 'histoendoscopy'. Further, while traditional views of classifying protruding and sessile lesions include those of Haggitt, the sm-classification, the Japanese and the so-called Vienna classifications to evaluate neoplasia, the development of new molecular techniques may give way to new methods of classifying preneoplasia and precancerous lesions. This review discusses some pros and cons of risk evaluation technologies in the colorectal tract by endoscopy, microscopy, and quantitative and molecular features. The morphometry-based studies performed over the past decades for the quantitative assessment of cellular and nuclear features within adenomas have failed to yield results amenable for clinical translation and are unlikely to improve further and gain widespread use with current technology. Rather, emerging knowledge of pathway-specific markers through the outlining of a molecular classification will likely be the basis for improved detection and diagnosis. The emerging genomic and proteomic technologies allowing for noninvasive tests to detect (asymptomatic) cancer and neoplasia are discussed. Lastly, the importance of recognizing bias and pitfalls and the adherence to guidelines for biomarker research are addressed.


The understanding of colorectal carcinogenesis has seen several advances over the past decades, ranging from improvements in endoscopic techniques to molecular understanding of colorectal cancer (CRC). The adenoma-carcinoma sequence has long been held as the accepted genetic model, yet recent findings point at distinct, separate genetic pathways involved in CRC.[1,2] Nonetheless, the colorectal polyp is still regarded as a precursor lesion in CRC. A polyp is defined as any lesion of the colorectal mucosa protruding into the lumen. Polyps in the colorectum are histologically classified as either hyperplastic or adenomatous, with various variants in between. Hyperplastic polyps in the colorectum have traditionally been regarded as non-neoplastic, but K-ras mutation is common, clonality has been demonstrated and biochemical abnormalities have been reported. This topic has received tremendous attention over the past decades, and it is now clear that the 'serrated adenoma' in hyperplastic polyps represents a distinct (epigenetically modulated) pathway in current colorectal carcinogenesis understanding.[1,2,3] This review aims to hightlight some new and emerging ways of assessing the malignant potential in colorectal lesions - from the endoscope to potential molecular markers.


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