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.
Keywords
Colorectal Cancer
Cowden Syndrome
Hamartomatous Polyposis
PTEN
Abbreviations used in this paper
CS
Cowden syndrome
GI
gastrointestinal
HPS
hyperplastic polyposis syndrome
ICC
International Cowden Consortium
PTEN
phosphatase and tensin homolog
SIR
standardized incidence ratio
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by grant P01CA124570 from the National Cancer Institute, the Doris Duke Distinguished Clinical Scientist Award, and the American Cancer Society Clinical Research Professorship, which was generously funded, in part, by the F.M. Kirby Foundation (all to C.E.).