Aberrant crypt foci of the colon as precursors of adenoma and cancer

N Engl J Med. 1998 Oct 29;339(18):1277-84. doi: 10.1056/NEJM199810293391803.


Background: Aberrant crypt foci of the colon are possible precursors of adenoma and cancer, but these lesions have been studied mainly in surgical specimens from patients who already had colon cancer.

Methods: Using magnifying endoscopy, we studied the prevalence, number, size, and dysplastic features of aberrant crypt foci and their distribution according to age in 171 normal subjects, 131 patients with adenoma, and 48 patients with colorectal cancer. We also prospectively examined the prevalence of aberrant crypt foci in 11 subjects (4 normal subjects, 6 with adenoma, and 1 with cancer) before and after the administration of 100 mg of sulindac three times a day for 8 to 12 months and compared the results with those in 9 untreated subjects (4 normal subjects and 5 with adenoma). All 20 subjects had aberrant crypt foci at base line.

Results: We identified 3155 aberrant crypt foci, 161 of which were dysplastic; the prevalence and number increased with age. There were significant (P<0.001) correlations between the number of aberrant crypt foci, the presence of dysplastic foci, the size of the foci, and the number of adenomas. After sulindac therapy, the number of foci decreased, disappearing in 7 of 11 subjects. In the untreated control group, the number of foci was unchanged in eight subjects and slightly increased in one (P<0.001 for the difference between the groups).

Conclusions: Aberrant crypt foci, particularly those that are large and have dysplastic features, may be precursors of adenoma and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / pathology
  • Adenoma / prevention & control
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Case-Control Studies
  • Colon / anatomy & histology
  • Colon / pathology*
  • Colonic Neoplasms / complications
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / prevention & control
  • Colonoscopy
  • Female
  • Genes, ras / genetics
  • Heart Diseases / complications
  • Heart Diseases / drug therapy
  • Humans
  • Male
  • Methylene Blue
  • Middle Aged
  • Osteoarthritis / complications
  • Osteoarthritis / drug therapy
  • Point Mutation
  • Precancerous Conditions / complications
  • Precancerous Conditions / drug therapy
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Prevalence
  • Prospective Studies
  • Sulindac / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Sulindac
  • Methylene Blue