Proximal aberrant crypt foci associate with synchronous neoplasia and are primed for neoplastic progression

David A. Drew, Allen Mo, James J. Grady, Richard G. Stevens, Joel B. Levine, Bruce M. Brenner, Joseph C. Anderson, Faripour Forouhar, Michael J. O'Brien, Thomas J. Devers, Daniel W. Rosenberg

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12- 6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas. Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma- carcinoma sequence but remain below the detection limit of conventional endoscopy. Visual Overview. Mol Cancer Res; 16(3); 486-95.

Original languageEnglish
Pages (from-to)486-495
Number of pages10
JournalMolecular Cancer Research
Issue number3
StatePublished - Mar 1 2018


Dive into the research topics of 'Proximal aberrant crypt foci associate with synchronous neoplasia and are primed for neoplastic progression'. Together they form a unique fingerprint.

Cite this