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Multiplicity and molecular heterogeneity of colorectal carcinomas in individuals with serrated polyposis.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2013 Mar; Vol. 37 (3), pp. 434-42. - Publication Year :
- 2013
-
Abstract
- Serrated polyposis (SP) is a clinically defined syndrome characterized by the occurrence of multiple serrated polyps in the large intestine. Individuals with SP and their relatives are at increased risk of colorectal carcinoma (CRC). We aimed to determine the pathologic and molecular profiles of CRCs in individuals fulfilling World Health Organization criteria for SP. A total of 45 CRCs were obtained from 38 individuals with SP (27 female and 11 male patients; median age at CRC diagnosis, 58.5 y) attending genetics clinics. Tumor samples were pathologically reviewed, screened for somatic BRAF and KRAS mutations, and analyzed immunohistochemically for mismatch repair protein (MMR) expression. Tumors were spread throughout the large intestine, with 64% located in the proximal colon. Mutations in BRAF and KRAS and immunohistochemical evidence of MMR deficiency were found in 46%, 5%, and 38%, respectively. Nearly half of CRCs were BRAF/KRAS wild type, and these were associated with distal location (63%) and MMR proficiency (84%). Overexpression of p53 and/or evidence of β-catenin activation were identified in 13 CRCs. Ten patients (26%) had synchronous or metachronous CRCs. In conclusion, the majority of CRCs arising in individuals with SP do not harbor molecular hallmarks of serrated pathway CRCs but show a diverse range of molecular profiles. The high proportion of multiple CRCs suggests that individuals with SP would benefit from frequent colonoscopic surveillance and from a consideration of a more extensive colectomy at the time of CRC diagnosis.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
Adolescent
Adult
Aged
Colonic Polyps genetics
Colonic Polyps pathology
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Female
Humans
Immunohistochemistry
Male
Middle Aged
Young Adult
Adenocarcinoma complications
Colonic Polyps complications
Colorectal Neoplasms complications
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 37
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23211288
- Full Text :
- https://doi.org/10.1097/PAS.0b013e318270f748