{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:43:26Z","timestamp":1790894606408,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,3,3]],"date-time":"2003-03-03T00:00:00Z","timestamp":1046649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2003,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The correlation between age at diagnosis and loss of expression of <jats:italic>hMLH1<\/jats:italic> protein in patients with colorectal carcinoma (CRC) has not been evaluated systematically.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Immunohistochemistry was performed for <jats:italic>hMLH1<\/jats:italic> protein in tumor samples from 867 patients with CRC. The authors defined tumors arising in the cecum, ascending colon, and transverse colon as right\u2010sided and tumors arising in the descending colon, sigmoid colon, and rectum as left\u2010sided. Patients' gender, tumor location (side), and <jats:italic>hMLH1<\/jats:italic> expression were analyzed by age groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The percentage of tumors with <jats:italic>hMLH1<\/jats:italic> expression loss increased significantly with advancing age (<jats:italic>P<\/jats:italic> &lt; 0.0001): There were no tumors in patients age &lt; 40 years that manifested loss of <jats:italic>hMLH1<\/jats:italic> expression, compared with 29% of tumors that manifested loss of <jats:italic>hMLH1<\/jats:italic> expression in patients age &gt; 90 years. Loss of <jats:italic>hMLH1<\/jats:italic> expression occurred more often in patients with right\u2010sided tumors (32.7% vs. 5.2% of patients with left\u2010sided tumors; <jats:italic>P<\/jats:italic> &lt; 0.0001) and in tumors from female patients (24.3% vs. 11.5% of tumors from male patients; <jats:italic>P<\/jats:italic> &lt; 0.0001). There was no evidence of interaction between gender and tumor location.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Loss of <jats:italic>hMLH1<\/jats:italic> expression in patients with CRC was associated strongly with increasing age. <jats:italic>hMLH1<\/jats:italic> expression loss was more pronounced in tumors from female patients and in tumors that originated on the right side of the colon. Loss of <jats:italic>hMLH1<\/jats:italic> expression in right\u2010sided tumors occurred in nearly 50% of patients age &gt; 90 years. This age\u2010related trend also was observed for males and in tumors that originated in the left colon. Cancer 2003;97:1421\u20137. \u00a9 2003 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.11206<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.11206","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T17:44:31Z","timestamp":1048009471000},"page":"1421-1427","source":"Crossref","is-referenced-by-count":84,"title":["Frequency of loss of <i>hMLH1<\/i> expression in colorectal carcinoma increases with advancing age"],"prefix":"10.1002","volume":"97","author":[{"given":"Sanjay","family":"Kakar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Burgart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen N.","family":"Thibodeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari G.","family":"Rabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria M.","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noralane M.","family":"Lindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,3,3]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"3455","article-title":"Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability","volume":"58","author":"Cunningham JM","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1999.0135"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.6870"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s005350070030"},{"key":"e_1_2_5_6_2","first-page":"6991","article-title":"Age\u2010related hypermethylation of the 5\u2032 region of MLH1 in normal colonic mucosa is associated with microsatellite\u2010unstable colorectal cancer development","volume":"61","author":"Nakagawa H","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60702-2"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.15.8681"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.710"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12661"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(99)80013-6"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8484122"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.4.1043"},{"key":"e_1_2_5_14_2","unstructured":"Surveillance Epidemiology and End Results (SEER) Program.Public\u2010use data (1973\u20131999) National Cancer Institute DCCPS Surveillance Research Program Cancer Statistics Branch[released April 2002; based on the November 2001 submission]. 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