Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers

Gastroenterology. 2010 Dec;139(6):1927-33. doi: 10.1053/j.gastro.2010.06.061. Epub 2010 Jun 27.


Background & aims: Germline phosphatase and tensin homolog (PTEN) mutations cause Cowden syndrome (CS), associated with breast and thyroid cancers. Case reports found 35%-85% of CS patients had gastrointestinal (GI) hamartomas. The association of benign and malignant GI neoplasias with CS remains debatable. Our goal is to describe the GI phenotype in a prospective series of PTEN mutation carriers.

Methods: Patients who met relaxed International Cowden Consortium criteria (N = 2548) or with 5 or more GI polyps, 1 or more of which was hyperplastic or hamartomatous (N = 397), were prospectively recruited. Germline PTEN mutation/deletion analysis was performed. Of the 2945 patients, 127 (123 of 2548 and 4 of 397, respectively) patients having clear pathogenic PTEN mutations were eligible for this study. Esophagogastroduodenoscopy, colonoscopy, and pathology reports were reviewed. The Fisher 2-tailed exact test, unpaired t tests, and age- and sex-adjusted standardized incidence ratio were calculated.

Results: Of 127 PTEN mutation carriers, 69 underwent 1 or more endoscopies with 64 (93%) having polyps. Of the 64, half had hyperplastic polyps. There were one to innumerable polyps in the colorectum, ileum, duodenum, stomach, and/or esophagus, with 24 subjects having both upper and lower GI polyps. Nine (13%) subjects had colorectal cancer, all younger than the age of 50. The adjusted standardized incidence ratio was 224.1 (95% confidence interval, 109.3-411.3; P < .0001).

Conclusions: PTEN-associated CS should be considered a mixed polyp syndrome, with hyperplastic polyps most prevalent, with a risk of early onset colorectal cancer. Routine colonoscopy should be considered in PTEN-associated CS, especially in the context of hyperplastic and/or adenomatous polyps.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Endoscopy, Gastrointestinal
  • Female
  • Gene Deletion
  • Hamartoma Syndrome, Multiple / epidemiology
  • Hamartoma Syndrome, Multiple / genetics*
  • Hamartoma Syndrome, Multiple / pathology
  • Humans
  • Infant
  • Intestinal Polyps / epidemiology
  • Intestinal Polyps / genetics*
  • Intestinal Polyps / pathology
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • Phenotype
  • Point Mutation
  • Risk Factors
  • Young Adult


  • PTEN Phosphohydrolase
  • PTEN protein, human