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CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients
CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I...
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Published in: | Modern pathology 2004-06, Vol.17 (6), p.711-721 |
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description | CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or ≥5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27Kip1 and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas. |
doi_str_mv | 10.1038/modpathol.3800110 |
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Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or ≥5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27Kip1 and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.3800110</identifier><identifier>PMID: 15073598</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>adenocarcinoma ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adult ; Aged ; Biomarkers - analysis ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; CD117 ; Cell Membrane - chemistry ; Cytoplasm - chemistry ; early stage ; Epithelial Cells - chemistry ; Female ; growth ; Humans ; Immunohistochemistry ; Laboratory Medicine ; lung ; Lung - chemistry ; Lung - pathology ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Mast Cells - chemistry ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Staging ; original-article ; Pathology ; Prognosis ; Proto-Oncogene Proteins c-kit - analysis ; squamous cell carcinoma ; survival ; Survival Analysis</subject><ispartof>Modern pathology, 2004-06, Vol.17 (6), p.711-721</ispartof><rights>2004 United States & Canadian Academy of Pathology</rights><rights>United States and Canadian Academy of Pathology, Inc. 2004</rights><rights>Copyright Nature Publishing Group Jun 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-2d1a23dd3a229a70d3e4aace93f93b1607e19faaa0d41f5fafff3bf5fdae36f53</citedby><cites>FETCH-LOGICAL-c484t-2d1a23dd3a229a70d3e4aace93f93b1607e19faaa0d41f5fafff3bf5fdae36f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15073598$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pelosi, Giuseppe</creatorcontrib><creatorcontrib>Barisella, Marta</creatorcontrib><creatorcontrib>Pasini, Felice</creatorcontrib><creatorcontrib>Leon, Maria Elena</creatorcontrib><creatorcontrib>Veronesi, Giulia</creatorcontrib><creatorcontrib>Spaggiari, Lorenzo</creatorcontrib><creatorcontrib>Fraggetta, Filippo</creatorcontrib><creatorcontrib>Iannucci, Antonio</creatorcontrib><creatorcontrib>Masullo, Michele</creatorcontrib><creatorcontrib>Sonzogni, Angelica</creatorcontrib><creatorcontrib>Maffini, Fausto</creatorcontrib><creatorcontrib>Viale, Giuseppe</creatorcontrib><title>CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or ≥5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27Kip1 and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.</description><subject>adenocarcinoma</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers - analysis</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>CD117</subject><subject>Cell Membrane - chemistry</subject><subject>Cytoplasm - chemistry</subject><subject>early stage</subject><subject>Epithelial Cells - chemistry</subject><subject>Female</subject><subject>growth</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Laboratory Medicine</subject><subject>lung</subject><subject>Lung - chemistry</subject><subject>Lung - pathology</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Mast Cells - chemistry</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>original-article</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-kit - analysis</subject><subject>squamous cell carcinoma</subject><subject>survival</subject><subject>Survival Analysis</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNp9kU1r3DAQhkVpaTZpf0APLaKH3Jzqw15b7alsvwKBXtqzmZVGGwVb2kjyQn5J_25lvGQhh5wkmGcezegl5B1nV5zJ7tMYzB7ybRiuZMcY5-wFWfFGsoqJrnlJVqxTspKqEWfkPKW7gtRNJ16TM96wVjaqW5F_m2-ct9SN4-RDRNDZHVx-oM7TlGGH9JqCQR80RO18GIGCNzTdTzCGKVGNw0BPtWBpvkU6TH73mUYc8ABeI82B7mPY-ZBcms1A07RNmGf-ib3s49Dn9Ia8sjAkfHs8L8jfH9__bH5VN79_Xm--3lS67upcCcNBSGMkCKGgZUZiDaBRSavklq9Zi1xZAGCm5raxYK2V23IxgHJtG3lBLhdvGfB-wpT70aV5K_BYFuxbrkSn2Ax-fALehSn6MlsvBOe1YuuuQHyBdAwpRbT9ProR4kPPWT9H1j9G1h8jKz0fjuJpO6I5dRwzKoBYgFRKfofx9PJz1vdLk4c8RXy0nupfljqWzz24Ik26fLxG4yLq3JvgnrH_B7Zyx08</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Pelosi, Giuseppe</creator><creator>Barisella, Marta</creator><creator>Pasini, Felice</creator><creator>Leon, Maria Elena</creator><creator>Veronesi, Giulia</creator><creator>Spaggiari, Lorenzo</creator><creator>Fraggetta, Filippo</creator><creator>Iannucci, Antonio</creator><creator>Masullo, Michele</creator><creator>Sonzogni, Angelica</creator><creator>Maffini, Fausto</creator><creator>Viale, Giuseppe</creator><general>Elsevier Inc</general><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>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>7X8</scope></search><sort><creationdate>20040601</creationdate><title>CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients</title><author>Pelosi, Giuseppe ; Barisella, Marta ; Pasini, Felice ; Leon, Maria Elena ; Veronesi, Giulia ; Spaggiari, Lorenzo ; Fraggetta, Filippo ; Iannucci, Antonio ; Masullo, Michele ; Sonzogni, Angelica ; Maffini, Fausto ; Viale, Giuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-2d1a23dd3a229a70d3e4aace93f93b1607e19faaa0d41f5fafff3bf5fdae36f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>adenocarcinoma</topic><topic>Adenocarcinoma - 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Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pelosi, Giuseppe</au><au>Barisella, Marta</au><au>Pasini, Felice</au><au>Leon, Maria Elena</au><au>Veronesi, Giulia</au><au>Spaggiari, Lorenzo</au><au>Fraggetta, Filippo</au><au>Iannucci, Antonio</au><au>Masullo, Michele</au><au>Sonzogni, Angelica</au><au>Maffini, Fausto</au><au>Viale, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>17</volume><issue>6</issue><spage>711</spage><epage>721</epage><pages>711-721</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or ≥5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27Kip1 and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>15073598</pmid><doi>10.1038/modpathol.3800110</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | adenocarcinoma Adenocarcinoma - metabolism Adenocarcinoma - pathology Adult Aged Biomarkers - analysis Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology CD117 Cell Membrane - chemistry Cytoplasm - chemistry early stage Epithelial Cells - chemistry Female growth Humans Immunohistochemistry Laboratory Medicine lung Lung - chemistry Lung - pathology Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Mast Cells - chemistry Medicine Medicine & Public Health Middle Aged Neoplasm Staging original-article Pathology Prognosis Proto-Oncogene Proteins c-kit - analysis squamous cell carcinoma survival Survival Analysis |
title | CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients |
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