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Sporadic Aberrant Crypt Foci Are Not a Surrogate Endpoint for Colorectal Adenoma Prevention

Authors' Affiliations: ¹ Department of Medicine and Arizona Cancer Center, University of Arizona, Tucson, Arizona and ² Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Correspondence: Requests for reprints: Peter Lance, Arizona Cancer Center, 1515 North Campbell Avenue, P.O. Box 245024, Tucson, AZ 85724-5024. Phone: 520-626-4492; Fax: 520-626-5348; E-mail: PLance{at}azcc.arizona.edu.

Abstract

Although colorectal cancer (CRC) remains the second most frequent cause of cancer-related death in industrialized countries, reductions in the numbers of deaths from this cancer are responsible for reductions in the total numbers of U.S. cancer deaths for the past 2 years (1). To understand the earliest identifiable precursors to this malignancy has been a decades-long goal of research to prevent CRC. The venerable concept of the adenoma-carcinoma sequence (2, 3) proposes that almost all CRCs develop from adenomatous epithelium or polyps (adenomas), i.e., visible lesions that protrude above the surrounding mucosal surface and are characterized histopathologically by the presence of intraepithelial neoplasia (dysplasia). Proposed more than four decades ago, this concept has evolved to include flat (nonpolypoid) adenomas and likely will require additional modification to include some types of serrated polyps (called "traditional serrated adenoma" and "sessile serrated adenoma") that lack the usual adenomatous epithelium but are uncommon precursors of CRC (4). The adenoma-carcinoma concept is otherwise essentially unscathed after many years of intensive study, and removing adenomas is an important CRC prevention strategy. Aberrant crypt foci (ACF) were identified as a result of research to describe the earliest morphologic precursor lesions. Since the late 1980s (5, 6), much effort has gone into aligning knowledge of the molecular pathogenesis of colorectal carcinogenesis with the sequential morphologic changes that take normal-appearing epithelial cells through stages of premalignant neoplastic change to become invasive CRCs. The seminal report "Aberrant Crypt Foci in the Adenoma Prevention with Celecoxib (APC) Trial" of Cho et al. (7) in this issue of the journal provides an important opportunity for putting ACF research into a new perspective.

Key Article

Aberrant Crypt Foci in the Adenoma Prevention with Celecoxib Trial

Nancy L. Cho, Mark Redston, Ann G. Zauber, Adelaide M. Carothers, Jason Hornick, Andrew Wilton, Stephen Sontag, Norman Nishioka, Francis M. Giardiello, John R. Saltzman, Chris Gostout, Craig J. Eagle, Ernest T. Hawk, and Monica M. Bertagnolli
Cancer Prevention Research 2008 0: 194062070. [Abstract]