Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells
Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival...
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| Veröffentlicht in: | Modern pathology 2013-08, Vol.26 (8), p.1123-1131 |
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| creator | Lee, Hee Jin Eom, Dae-Woon Kang, Gil Hyun Han, Sang Hak Cheon, Gab Jin Oh, Ho-Suk Han, Koon Hee Ahn, Heui June Jang, Hyuk-Jai Han, Myoung Sik |
| description | Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (
P |
| doi_str_mv | 10.1038/modpathol.2012.163 |
| format | Article |
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P
<0.0001) and lymph node metastasis (
P
<0.0001), higher pathological T and tumor node metastasis stages (
P
=0.047 and
P
=0.001), and more frequent SOX2 (
P
=0.038) and NOTCH3 expressions (
P
=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%,
P
<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (
P
<0.0001) and multivariate (
P
=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2012.163</identifier><identifier>PMID: 23060121</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/67/1857 ; 631/67/71 ; 692/699/67/1504/1885 ; 692/700/1750 ; Adenocarcinoma, Papillary - genetics ; Adenocarcinoma, Papillary - mortality ; Adenocarcinoma, Papillary - pathology ; Aged ; Biomarkers, Tumor - analysis ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Female ; Hospitals ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Laboratory Medicine ; Lymphatic system ; Male ; Medical prognosis ; Medical schools ; Medicine ; Medicine & Public Health ; Metastasis ; Microsatellite Instability ; Middle Aged ; Neoplastic Stem Cells - pathology ; original-article ; Pathology ; Prognosis ; Proportional Hazards Models ; Stem cells ; Survival analysis ; Tissue Array Analysis ; Tumors</subject><ispartof>Modern pathology, 2013-08, Vol.26 (8), p.1123-1131</ispartof><rights>United States & Canadian Academy of Pathology 2013</rights><rights>Copyright Nature Publishing Group Aug 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-fd6a383cb808ea3efd7b36ddf54fb32f03a0a3edc52ea5315b8a844161a0d55d3</citedby><cites>FETCH-LOGICAL-c419t-fd6a383cb808ea3efd7b36ddf54fb32f03a0a3edc52ea5315b8a844161a0d55d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1416106406?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23060121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hee Jin</creatorcontrib><creatorcontrib>Eom, Dae-Woon</creatorcontrib><creatorcontrib>Kang, Gil Hyun</creatorcontrib><creatorcontrib>Han, Sang Hak</creatorcontrib><creatorcontrib>Cheon, Gab Jin</creatorcontrib><creatorcontrib>Oh, Ho-Suk</creatorcontrib><creatorcontrib>Han, Koon Hee</creatorcontrib><creatorcontrib>Ahn, Heui June</creatorcontrib><creatorcontrib>Jang, Hyuk-Jai</creatorcontrib><creatorcontrib>Han, Myoung Sik</creatorcontrib><title>Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (
P
<0.0001) and lymph node metastasis (
P
<0.0001), higher pathological T and tumor node metastasis stages (
P
=0.047 and
P
=0.001), and more frequent SOX2 (
P
=0.038) and NOTCH3 expressions (
P
=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%,
P
<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (
P
<0.0001) and multivariate (
P
=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.</description><subject>631/67/1857</subject><subject>631/67/71</subject><subject>692/699/67/1504/1885</subject><subject>692/700/1750</subject><subject>Adenocarcinoma, Papillary - genetics</subject><subject>Adenocarcinoma, Papillary - mortality</subject><subject>Adenocarcinoma, Papillary - pathology</subject><subject>Aged</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Female</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Laboratory Medicine</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastasis</subject><subject>Microsatellite Instability</subject><subject>Middle Aged</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>original-article</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Stem cells</subject><subject>Survival analysis</subject><subject>Tissue Array Analysis</subject><subject>Tumors</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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>eNp1kV1LwzAYhYMoOqd_wAsJeONNZz6aLr2U4RcMvNHr8jZJt8y2qUmL7N-bsjlE8CqQPOfkvO9B6IqSGSVc3jVOd9CvXT1jhLIZzfgRmlDBSUKYFMdoQmTOE54LdobOQ9gQQlMh2Sk6Y5xkUUInqFm42nmjeqhxY5V3HXS2rsFvsQKvbOsaCBi8wRCCUxZ6o_GX7de4c87jzrtV64KNSKuxab1V6wjYFjfgP4wP2FU49KbBytR1uEAnFdTBXO7PKXp_fHhbPCfL16eXxf0yUSnN-6TSGXDJVSmJNMBNpeclz7SuRFqVnFWEA4nXWglmQHAqSgkyTWlGgWghNJ-i251vzPc5mNAXjQ1jAmiNG0JBUzoXbJ7naURv_qAbN_g2phupjJIsJVmk2I6KGwrBm6rovI0jbgtKirGM4lBGMZZRxDKi6HpvPZSN0QfJz_YjwHdAiE_tyvhff_9v-w11pZs9</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Lee, Hee Jin</creator><creator>Eom, Dae-Woon</creator><creator>Kang, Gil Hyun</creator><creator>Han, Sang Hak</creator><creator>Cheon, Gab Jin</creator><creator>Oh, Ho-Suk</creator><creator>Han, Koon Hee</creator><creator>Ahn, Heui June</creator><creator>Jang, Hyuk-Jai</creator><creator>Han, Myoung Sik</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><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>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20130801</creationdate><title>Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells</title><author>Lee, Hee Jin ; Eom, Dae-Woon ; Kang, Gil Hyun ; Han, Sang Hak ; Cheon, Gab Jin ; Oh, Ho-Suk ; Han, Koon Hee ; Ahn, Heui June ; Jang, Hyuk-Jai ; Han, Myoung Sik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-fd6a383cb808ea3efd7b36ddf54fb32f03a0a3edc52ea5315b8a844161a0d55d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/67/1857</topic><topic>631/67/71</topic><topic>692/699/67/1504/1885</topic><topic>692/700/1750</topic><topic>Adenocarcinoma, Papillary - genetics</topic><topic>Adenocarcinoma, Papillary - mortality</topic><topic>Adenocarcinoma, Papillary - pathology</topic><topic>Aged</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Female</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Laboratory Medicine</topic><topic>Lymphatic system</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Microsatellite Instability</topic><topic>Middle Aged</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>original-article</topic><topic>Pathology</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Stem cells</topic><topic>Survival analysis</topic><topic>Tissue Array Analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hee Jin</creatorcontrib><creatorcontrib>Eom, Dae-Woon</creatorcontrib><creatorcontrib>Kang, Gil Hyun</creatorcontrib><creatorcontrib>Han, Sang Hak</creatorcontrib><creatorcontrib>Cheon, Gab Jin</creatorcontrib><creatorcontrib>Oh, Ho-Suk</creatorcontrib><creatorcontrib>Han, Koon Hee</creatorcontrib><creatorcontrib>Ahn, Heui June</creatorcontrib><creatorcontrib>Jang, Hyuk-Jai</creatorcontrib><creatorcontrib>Han, Myoung Sik</creatorcontrib><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>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hee Jin</au><au>Eom, Dae-Woon</au><au>Kang, Gil Hyun</au><au>Han, Sang Hak</au><au>Cheon, Gab Jin</au><au>Oh, Ho-Suk</au><au>Han, Koon Hee</au><au>Ahn, Heui June</au><au>Jang, Hyuk-Jai</au><au>Han, Myoung Sik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2013-08-01</date><risdate>2013</risdate><volume>26</volume><issue>8</issue><spage>1123</spage><epage>1131</epage><pages>1123-1131</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (
P
<0.0001) and lymph node metastasis (
P
<0.0001), higher pathological T and tumor node metastasis stages (
P
=0.047 and
P
=0.001), and more frequent SOX2 (
P
=0.038) and NOTCH3 expressions (
P
=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%,
P
<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (
P
<0.0001) and multivariate (
P
=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23060121</pmid><doi>10.1038/modpathol.2012.163</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | 631/67/1857 631/67/71 692/699/67/1504/1885 692/700/1750 Adenocarcinoma, Papillary - genetics Adenocarcinoma, Papillary - mortality Adenocarcinoma, Papillary - pathology Aged Biomarkers, Tumor - analysis Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - mortality Colorectal Neoplasms - pathology Female Hospitals Humans Immunohistochemistry Kaplan-Meier Estimate Laboratory Medicine Lymphatic system Male Medical prognosis Medical schools Medicine Medicine & Public Health Metastasis Microsatellite Instability Middle Aged Neoplastic Stem Cells - pathology original-article Pathology Prognosis Proportional Hazards Models Stem cells Survival analysis Tissue Array Analysis Tumors |
| title | Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells |
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