Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps

Tsung Teh Wu, Banafsheh Rezai, Asif Rashid, Michael C. Luce, Matt C. Cayouette, Christopher Kim, Nirmal Sani, Lopa Mishra, Christopher A. Moskaluk, John H. Yardley, Stanley R. Hamilton

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Juvenile polyps are regarded as hamartomatous polyps and occur in .sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyps from 12 patients with juvenile polyposts syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21 (WAFI/CIP1) seen in native colerectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposts coil (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colerectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.

Original languageEnglish (US)
Pages (from-to)939-947
Number of pages9
JournalAmerican Journal of Pathology
Volume150
Issue number3
StatePublished - 1997
Externally publishedYes

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Polyps
Juvenile polyposis syndrome
Cyclin-Dependent Kinase Inhibitor p21
Neoplasms
Mutation
p53 Genes
Epithelium
Staining and Labeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Wu, T. T., Rezai, B., Rashid, A., Luce, M. C., Cayouette, M. C., Kim, C., ... Hamilton, S. R. (1997). Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. American Journal of Pathology, 150(3), 939-947.

Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. / Wu, Tsung Teh; Rezai, Banafsheh; Rashid, Asif; Luce, Michael C.; Cayouette, Matt C.; Kim, Christopher; Sani, Nirmal; Mishra, Lopa; Moskaluk, Christopher A.; Yardley, John H.; Hamilton, Stanley R.

In: American Journal of Pathology, Vol. 150, No. 3, 1997, p. 939-947.

Research output: Contribution to journalArticle

Wu, TT, Rezai, B, Rashid, A, Luce, MC, Cayouette, MC, Kim, C, Sani, N, Mishra, L, Moskaluk, CA, Yardley, JH & Hamilton, SR 1997, 'Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps', American Journal of Pathology, vol. 150, no. 3, pp. 939-947.
Wu, Tsung Teh ; Rezai, Banafsheh ; Rashid, Asif ; Luce, Michael C. ; Cayouette, Matt C. ; Kim, Christopher ; Sani, Nirmal ; Mishra, Lopa ; Moskaluk, Christopher A. ; Yardley, John H. ; Hamilton, Stanley R. / Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. In: American Journal of Pathology. 1997 ; Vol. 150, No. 3. pp. 939-947.
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