TY - JOUR
T1 - Screening for defective DNA mismatch repair in stage II and III colorectal cancer patients
AU - Chai, S.M.
AU - Zeps, Nikolajs
AU - Shearwood, A-M.
AU - Grieu, F.
AU - Charles, Adrian
AU - Harvey, Jennet
AU - Goldblatt, J.
AU - Joseph, D.
AU - Iacopetta, Barry
PY - 2004
Y1 - 2004
N2 - Background & Aims: Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome usually present in younger patients, show loss of mismatch repair (MMR) gene expression, and exhibit microsatellite instability (MSI). About 12% of sporadic colorectal cancers also show MMR loss and MSI. The aims of this study were to evaluate MMR loss and MSI in relation to patient age, sex, tumor stage, and site in the large bowel. Methods: Tissue microarrays were created from 1020 stage II and III colorectal cancer cases and immunohistochemical staining performed to detect expression of the 2 major MMR proteins, hMLH1 and hMSH2. MSI was determined using the BAT-26 mononucleotide repeat. Results: Ten percent of tumors showed loss of hMLH1 expression and 1.2% showed loss of hMSH2 expression. hMLH1 loss was more frequent in women (P <.001), older patients (P = .004), earlier stage tumors (P = .0001), and proximal colon tumors (P <.0001). In contrast, tumors showing hMSH2 loss were more frequent in younger (P <.001), male (P = .05) patients and were distributed evenly between the proximal colon and distal colon/rectum. Eleven percent of tumors were MSI+ and these showed similar age, sex, stage, and site characteristics as tumors with hMLH1 loss. Discordance between MMR loss and MSI+ was found in 24 of 983 (2.4%) tumors. Of the 231 patients aged
AB - Background & Aims: Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome usually present in younger patients, show loss of mismatch repair (MMR) gene expression, and exhibit microsatellite instability (MSI). About 12% of sporadic colorectal cancers also show MMR loss and MSI. The aims of this study were to evaluate MMR loss and MSI in relation to patient age, sex, tumor stage, and site in the large bowel. Methods: Tissue microarrays were created from 1020 stage II and III colorectal cancer cases and immunohistochemical staining performed to detect expression of the 2 major MMR proteins, hMLH1 and hMSH2. MSI was determined using the BAT-26 mononucleotide repeat. Results: Ten percent of tumors showed loss of hMLH1 expression and 1.2% showed loss of hMSH2 expression. hMLH1 loss was more frequent in women (P <.001), older patients (P = .004), earlier stage tumors (P = .0001), and proximal colon tumors (P <.0001). In contrast, tumors showing hMSH2 loss were more frequent in younger (P <.001), male (P = .05) patients and were distributed evenly between the proximal colon and distal colon/rectum. Eleven percent of tumors were MSI+ and these showed similar age, sex, stage, and site characteristics as tumors with hMLH1 loss. Discordance between MMR loss and MSI+ was found in 24 of 983 (2.4%) tumors. Of the 231 patients aged
U2 - 10.1016/S1542-3565(04)00451-3
DO - 10.1016/S1542-3565(04)00451-3
M3 - Article
SN - 1542-3565
VL - 2
SP - 1017
EP - 1025
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - NA
ER -
