{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T18:23:43Z","timestamp":1781893423428,"version":"3.54.5"},"reference-count":35,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2000,7,18]]},"published-print":{"date-parts":[[2001,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>It has yet to be established whether proliferative activity in the macroscopically normal colonic mucosa is causally correlated with neoplastic risk. Measurement of proliferative activity in human subjects is of necessity usually undertaken using indirect methods with inherent limitations, and relatively little has been published on the effect of normal biological variables on such indices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>AIMS<\/jats:title>\n                    <jats:p>To establish the validity of mitosis counts following whole crypt microdissection as an index of the crypt cell proliferative state (CCPS) and to examine the effect of normal biological variables (age, sex, and colonic site) and colonic neoplasia on the mitotic index in macroscopically normal human colon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUBJECTS<\/jats:title>\n                    <jats:p>Mucosal samples were obtained at colectomy or colonoscopy from 107 individuals (24 controls, 23 sporadic adenoma patients, 31 sporadic carcinoma patients, and 29 patients with familial adenomatous polyposis (FAP)).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"methods\">\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Mucosal specimens were hydrated, hydrolysed, and small groups of crypts separated from the main specimen under a dissecting microscope. The total number of mitoses\/crypt were counted by one observer for each of 10 complete crypts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Validation work established that whole crypt mitoses counts were reliable and reproducible. There was no relation between age and mean mitoses\/crypt (Pearson correlation coefficient \u22120.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80\u20134.66)) among controls but there was no gender difference in the three disease groups. For all disease groups and controls, the crypt mitotic count showed a significant linear increase (p=0.004) from the rectum to the caecum. Biopsies from within 5 cm of the macroscopic margin of a carcinoma (near) gave a mean mitosis count of 12.6 while those from more than 10 cm (far) were lower but not significantly so (p=0.12) with a count of 9.0. The mean mitoses\/crypt were similar for the controls and adenomas (5.6 and 4.7, respectively) but greater for the cancers and especially for FAP (8.3 and 14.2, respectively). Statistical analysis confirmed that there were significant differences (p&lt;0.05) between controls and all disease groups together, between sporadic disease and FAP, and between adenoma and carcinoma subjects at each of the four colonic sites. Post hoc comparison by\n                      <jats:italic>t<\/jats:italic>\n                      test showed significantly greater CCPS for FAP compared with controls (p&lt;0.001) and for sporadic cancer versus controls (p=0.04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Whole crypt microdissection and mitosis counting is a reliable, reproducible, and robust technique for assessing CCPS in the human colon. CCPS is unaffected by age but increases from the distal to the proximal colon. CCPS is increased if a sporadic cancer is present and markedly increased in FAP. However, the precise relation of an increased CCPS to the neoplastic process remains uncertain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gut.48.1.41","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:32:32Z","timestamp":1027751552000},"page":"41-46","source":"Crossref","is-referenced-by-count":51,"title":["Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis"],"prefix":"10.1136","volume":"48","author":[{"given":"S J","family":"Mills","sequence":"first","affiliation":[{"name":"aHuman Nutrition Research Centre, Department of Biological and Nutritional Sciences, The University, Newcastle upon Tyne NE1 7RU, UK, \n\nbHuman Nutrition Research Centre, Department of Human Genetics, The University, Newcastle upon Tyne NE1 7RU, UK, \n\ncWansbeck District General Hospital Trust, Woodhorn Lane, Ashington NE63 9JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Mathers","sequence":"additional","affiliation":[{"name":"aHuman Nutrition Research Centre, Department of Biological and Nutritional Sciences, The University, Newcastle upon Tyne NE1 7RU, UK, \n\nbHuman Nutrition Research Centre, Department of Human Genetics, The University, Newcastle upon Tyne NE1 7RU, UK, \n\ncWansbeck District General Hospital Trust, Woodhorn Lane, Ashington NE63 9JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P D","family":"Chapman","sequence":"additional","affiliation":[{"name":"aHuman Nutrition Research Centre, Department of Biological and Nutritional Sciences, The University, Newcastle upon Tyne NE1 7RU, UK, \n\nbHuman Nutrition Research Centre, Department of Human Genetics, The University, Newcastle upon Tyne NE1 7RU, UK, \n\ncWansbeck District General Hospital Trust, Woodhorn Lane, Ashington NE63 9JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Burn","sequence":"additional","affiliation":[{"name":"aHuman Nutrition Research Centre, Department of Biological and Nutritional Sciences, The University, Newcastle upon Tyne NE1 7RU, UK, \n\nbHuman Nutrition Research Centre, Department of Human Genetics, The University, Newcastle upon Tyne NE1 7RU, UK, \n\ncWansbeck District General Hospital Trust, Woodhorn Lane, Ashington NE63 9JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Gunn","sequence":"additional","affiliation":[{"name":"aHuman Nutrition Research Centre, Department of Biological and Nutritional Sciences, The University, Newcastle upon Tyne NE1 7RU, UK, \n\nbHuman Nutrition Research Centre, Department of Human Genetics, The University, Newcastle upon Tyne NE1 7RU, UK, \n\ncWansbeck District General Hospital Trust, Woodhorn Lane, Ashington NE63 9JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2001,1,1]]},"reference":[{"key":"2025121305472550000_48.1.41.1","first-page":"279","article-title":"Expansion of the epithelial cell proliferative compartment and frequency of adenomatous polyps in the colon correlate with the strength of family history of colorectal cancer.","volume":"53","author":"Gerdes","year":"1993","journal-title":"Cancer Res"},{"key":"2025121305472550000_48.1.41.2","first-page":"4201","article-title":"Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells.","volume":"44","author":"Lipkin","year":"1984","journal-title":"Cancer Res"},{"key":"2025121305472550000_48.1.41.3","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19880601)61:11<2286::AID-CNCR2820611124>3.0.CO;2-K"},{"key":"2025121305472550000_48.1.41.4","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)90019-H"},{"key":"2025121305472550000_48.1.41.5","doi-asserted-by":"publisher","DOI":"10.1136\/gut.33.4.524"},{"key":"2025121305472550000_48.1.41.6","first-page":"1899","article-title":"Tritiated thymidine labelling distribution as a marker for hereditary predisposition to colon cancer.","volume":"43","author":"Lipkin","year":"1983","journal-title":"Cancer Res"},{"key":"2025121305472550000_48.1.41.7","unstructured":"Goodlad RA (1994) Microdissection-based techniques for the determination of cell proliferation in gastrointestinal epithelium: application to animal and human studies. in Cell biology: A laboratory handbook. ed Celis JE (Academic Press Inc. 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