Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis
BACKGROUND 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...
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| description | BACKGROUND 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. AIMS 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. SUBJECTS 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)). METHODS 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. RESULTS 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 −0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80–4.66)) 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 |
| doi_str_mv | 10.1136/gut.48.1.41 |
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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. AIMS 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. SUBJECTS 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)). METHODS 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. RESULTS 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 −0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80–4.66)) 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<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 byt test showed significantly greater CCPS for FAP compared with controls (p<0.001) and for sporadic cancer versus controls (p=0.04). CONCLUSIONS 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.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>EISSN: 1458-3288</identifier><identifier>DOI: 10.1136/gut.48.1.41</identifier><identifier>PMID: 11115821</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Adenoma - pathology ; Adenomatous Polyposis Coli - pathology ; Adult ; Aged ; Analysis of Variance ; Apoptosis ; Biological and medical sciences ; Biopsy ; Carcinoma - pathology ; Case-Control Studies ; Causes of ; Cell growth ; Cell proliferation ; Colon - pathology ; colonic crypt ; Colonic Neoplasms - pathology ; Colorectal cancer ; Digestive system ; Dissection ; Ethanol ; familial adenomatous polyposis ; Female ; Human subjects ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical research ; Medical sciences ; Methods ; Middle Aged ; Mitotic Index ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Physiological aspects ; Polyposis, Familial ; Rectum - pathology ; Reproducibility of Results ; Studies ; Surveillance ; Tumors</subject><ispartof>Gut, 2001-01, Vol.48 (1), p.41-46</ispartof><rights>British Society of Gastroenterology</rights><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 BMJ Publishing Group Ltd.</rights><rights>Copyright: 2001 British Society of Gastroenterology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b604t-f1906c2b3b30b68590d4759f5ba2becf7aa7a96d468d7b5812884866bd7ba973</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1728170/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1728170/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=859221$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11115821$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mills, S J</creatorcontrib><creatorcontrib>Mathers, J C</creatorcontrib><creatorcontrib>Chapman, P D</creatorcontrib><creatorcontrib>Burn, J</creatorcontrib><creatorcontrib>Gunn, A</creatorcontrib><title>Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis</title><title>Gut</title><addtitle>Gut</addtitle><description>BACKGROUND 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. AIMS 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. SUBJECTS 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)). METHODS 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. RESULTS 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 −0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80–4.66)) 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<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 byt test showed significantly greater CCPS for FAP compared with controls (p<0.001) and for sporadic cancer versus controls (p=0.04). CONCLUSIONS 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.</description><subject>Adenoma - pathology</subject><subject>Adenomatous Polyposis Coli - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Carcinoma - pathology</subject><subject>Case-Control Studies</subject><subject>Causes of</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Colon - pathology</subject><subject>colonic crypt</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Digestive system</subject><subject>Dissection</subject><subject>Ethanol</subject><subject>familial adenomatous polyposis</subject><subject>Female</subject><subject>Human subjects</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Methods</subject><subject>Middle Aged</subject><subject>Mitotic Index</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Physiological aspects</subject><subject>Polyposis, Familial</subject><subject>Rectum - pathology</subject><subject>Reproducibility of Results</subject><subject>Studies</subject><subject>Surveillance</subject><subject>Tumors</subject><issn>0017-5749</issn><issn>1468-3288</issn><issn>1458-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kk2P0zAQhiMEYsvCiTuKQOICKXbixM4FaVXxJa3gUvXAxRonTtfFsYOdAP0F_G2m26pbUEUSyXLm8euZdyZJnlIyp7So3qyncc7EnM4ZvZfMKKtEVuRC3E9mhFCelZzVF8mjGDeEECFq-jC5oPiUIqez5PfCW-9MkzZhO4xpo61Nh-Ct6XSA0XiXxhFGnUKMGr82Vdv05423-nCgN03wrcFQc0sbPDD4AC1KOu0HC9FACq5NO-iNNWBTaLXzPYx-iung7Xbw0cTHyYMObNRPDutlsnz_brn4mF1_-fBpcXWdqYqwMetoTaomV4UqiKpEWZOW8bLuSgW50k3HATjUVYsmtFyVgqIRTFSVwh3UvLhM3u5lh0n1um20GwNYOQTTQ9hKD0b-HXHmRq79D0l5LignKPDyIBD890nHUfYm7lwDrHaKkpOSoc8Fgi_-ATd-Cg5rQy1e11iOoEg931NrsFoa13m8tdlJyisuCKtJkSP0-gy01g5bhM3TncHfp3h2Bse31ditc_yrPY-djDHo7mgHJXI3YRInTDIhqWS7jJ-dOnjHHkbqpHCIDdgugGtMPHLYs_yWOiRp4qh_HaMQvsmKF7yUn1cL-bUkq9VKLCW_8131m__m9wcYz_b8</recordid><startdate>200101</startdate><enddate>200101</enddate><creator>Mills, S J</creator><creator>Mathers, J C</creator><creator>Chapman, P D</creator><creator>Burn, J</creator><creator>Gunn, A</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ</general><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200101</creationdate><title>Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis</title><author>Mills, S J ; Mathers, J C ; Chapman, P D ; Burn, J ; Gunn, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b604t-f1906c2b3b30b68590d4759f5ba2becf7aa7a96d468d7b5812884866bd7ba973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adenoma - pathology</topic><topic>Adenomatous Polyposis Coli - pathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Analysis of Variance</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Carcinoma - pathology</topic><topic>Case-Control Studies</topic><topic>Causes of</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Colon - pathology</topic><topic>colonic crypt</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Digestive system</topic><topic>Dissection</topic><topic>Ethanol</topic><topic>familial adenomatous polyposis</topic><topic>Female</topic><topic>Human subjects</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Methods</topic><topic>Middle Aged</topic><topic>Mitotic Index</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Physiological aspects</topic><topic>Polyposis, Familial</topic><topic>Rectum - pathology</topic><topic>Reproducibility of Results</topic><topic>Studies</topic><topic>Surveillance</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mills, S J</creatorcontrib><creatorcontrib>Mathers, J C</creatorcontrib><creatorcontrib>Chapman, P D</creatorcontrib><creatorcontrib>Burn, J</creatorcontrib><creatorcontrib>Gunn, A</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mills, S J</au><au>Mathers, J C</au><au>Chapman, P D</au><au>Burn, J</au><au>Gunn, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2001-01</date><risdate>2001</risdate><volume>48</volume><issue>1</issue><spage>41</spage><epage>46</epage><pages>41-46</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><eissn>1458-3288</eissn><coden>GUTTAK</coden><abstract>BACKGROUND 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. AIMS 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. SUBJECTS 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)). METHODS 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. RESULTS 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 −0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80–4.66)) 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<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 byt test showed significantly greater CCPS for FAP compared with controls (p<0.001) and for sporadic cancer versus controls (p=0.04). CONCLUSIONS 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.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>11115821</pmid><doi>10.1136/gut.48.1.41</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoma - pathology Adenomatous Polyposis Coli - pathology Adult Aged Analysis of Variance Apoptosis Biological and medical sciences Biopsy Carcinoma - pathology Case-Control Studies Causes of Cell growth Cell proliferation Colon - pathology colonic crypt Colonic Neoplasms - pathology Colorectal cancer Digestive system Dissection Ethanol familial adenomatous polyposis Female Human subjects Humans Investigative techniques, diagnostic techniques (general aspects) Male Medical research Medical sciences Methods Middle Aged Mitotic Index Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Physiological aspects Polyposis, Familial Rectum - pathology Reproducibility of Results Studies Surveillance Tumors |
| title | Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis |
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