TY - JOUR
T1 - Multiplicity and molecular heterogeneity of colorectal carcinomas in individuals with serrated polyposis
AU - Rosty, C.
AU - Walsh, M.D.
AU - Walters, R.J.
AU - Clendenning, M.
AU - Pearson, S.A.
AU - Jenkins, M.A.
AU - Win, A.K.O.
AU - Hopper, J.L.
AU - Sweet, K.M.
AU - Frankel, W.L.
AU - Aronson, M.D.
AU - Gallinger, S.S.
AU - Goldblatt, Jack
AU - Tucker, K.
AU - Greening, S.
AU - Gattas, M.R.
AU - Woodall, S.
AU - Arnold, J.L.
AU - Walker, N.I.
AU - Parry, S.
AU - Young, J.P.
AU - Buchanan, D.D.
PY - 2013
Y1 - 2013
N2 - 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. Copyright © 2013 by Lippincott Williams & Wilkins.
AB - 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. Copyright © 2013 by Lippincott Williams & Wilkins.
U2 - 10.1097/PAS.0b013e318270f748
DO - 10.1097/PAS.0b013e318270f748
M3 - Article
C2 - 23211288
SN - 0147-5185
VL - 37
SP - 434
EP - 442
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 3
ER -