Diversity Counts

Danielle Langeveld, Marnix Jansen, Lodewijk Brosens, Folkert Morsink, G. Johan Offerhaus, Wendy de Leng
2011 American Journal of Clinical Pathology  
A b s t r a c t Tumor progression is critically dependent on the selection of genetic alterations. This clonal evolution can be traced to the stage preceding visible tumor formation called pretumor progression, in which genetic change occurs without visible change. Recently, the identification of intestinal stem cell markers in animal models has made visualization of stem cells possible in vivo. Translating this work to the clinical setting by visualizing stem cells in patient material may
more » ... us to understand differences in patients' vulnerability to cancer development and target preventive measures to high-risk groups. In this review article, we examine some of the analytic methods currently used in research settings tracing stem cell dynamics. From a genetic viewpoint, the initiation and progression of colorectal cancer is one of the best understood examples of malignant derailment in current oncologic practice. This progress can largely be attributed to a clear understanding of the histologic lesions that precede the invasive colorectal cancer. The removal of preinvasive dysplastic lesions in affected patients is expected to reduce neoplastic progression and, therefore, decrease morbidity. Lesions that are treated later in the course of the disease often require invasive surgery and, possibly, adjuvant chemotherapeutic treatment. Therefore, much of our efforts are devoted to properly identifying and classifying these precursor lesions. The adenoma-carcinoma sequence describes the stepwise progression from normal to dysplastic adenomatous epithelium and, eventually, invasive cancer due to a series of genetic changes. 1 This model has been the driving force behind colorectal cancer research for more than 2 decades. More recently, attention has been given to alternative models of tumor initiation and progression, most notably the so-called serrated pathway to neoplasia. These models show that colorectal cancer is not a linear "one pathway" disease but that it can develop in multiple ways. Most precursor lesions (traditional adenomas or serrated adenomas) develop only after the age of 50 years, suggesting that little occurs before this stage because there are no visible lesions in the colorectum that may be targeted endoscopically. However, even patients affected by cancer susceptibility syndromes such as Li-Fraumeni or familial adenomatous polyposis (FAP; due to a germline p53 or an APC mutation, respectively) have normal histologic findings early in the course of their disease despite having a (potentially) hazardous genetic mutation. Upon completion of this activity you will be able to: • define and discuss the concept of pretumor progression. • describe how pretumor progression can be established in the colon. • explain why an estimate of the rate of pretumor progression is essential to establish risk assessment. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 975. Exam is located at www.ascp.org/ajcpcme.
doi:10.1309/ajcpp3i5hdywmhja pmid:21571961 fatcat:tegle5ohyzf5hnm3kq2xon7xiq