p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors
Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been system...
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| Veröffentlicht in: | Modern pathology 2004-01, Vol.17 (1), p.33-39 |
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| description | Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2–12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2–15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2–80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (P |
| doi_str_mv | 10.1038/modpathol.3800009 |
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Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2–12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2–15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2–80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (P<0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity × percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (P<0.05). Finally, a Bcl-x : Bax ratio ≥1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio ≥1 (P<0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.3800009</identifier><identifier>PMID: 14631373</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>Antibodies ; Apoptosis ; Apoptosis Regulatory Proteins - analysis ; Bax ; Bcl-2 ; bcl-2-Associated X Protein - analysis ; Bcl-x ; bcl-X Protein - analysis ; carcinoid tumor ; Cell Proliferation ; Enzymes ; Follow-Up Studies ; Georgia ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen - analysis ; Laboratory Medicine ; London ; mediastinum ; Medicine ; Medicine & Public Health ; MIB-1 cellular proliferation ; Morphology ; Neoplasm Staging ; neuroendocrine carcinoma ; Neuroendocrine tumors ; Neuroendocrine Tumors - chemistry ; Neuroendocrine Tumors - immunology ; Neuroendocrine Tumors - mortality ; Neuroendocrine Tumors - pathology ; Neuroendocrine Tumors - therapy ; Odds Ratio ; original-article ; p53 ; Pathology ; Proto-Oncogene Proteins c-bcl-2 - analysis ; Risk Assessment ; thymus ; Thymus gland ; Thymus Neoplasms - chemistry ; Thymus Neoplasms - immunology ; Thymus Neoplasms - mortality ; Thymus Neoplasms - pathology ; Thymus Neoplasms - therapy ; Time Factors ; Treatment Outcome ; Tumor Suppressor Protein p53 - analysis</subject><ispartof>Modern pathology, 2004-01, Vol.17 (1), p.33-39</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 Jan 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-236412845782173e780466954ac0020425d71b40b3f66792aeba0163f2cfbf733</citedby><cites>FETCH-LOGICAL-c550t-236412845782173e780466954ac0020425d71b40b3f66792aeba0163f2cfbf733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/221214546?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,778,782,27911,27912,64370,64372,64374,72224</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14631373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gal, Anthony A</creatorcontrib><creatorcontrib>Sheppard, Mary N</creatorcontrib><creatorcontrib>Nolen, John D L</creatorcontrib><creatorcontrib>Cohen, Cynthia</creatorcontrib><title>p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2–12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2–15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2–80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (P<0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity × percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (P<0.05). Finally, a Bcl-x : Bax ratio ≥1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio ≥1 (P<0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - analysis</subject><subject>Bax</subject><subject>Bcl-2</subject><subject>bcl-2-Associated X Protein - analysis</subject><subject>Bcl-x</subject><subject>bcl-X Protein - analysis</subject><subject>carcinoid tumor</subject><subject>Cell Proliferation</subject><subject>Enzymes</subject><subject>Follow-Up Studies</subject><subject>Georgia</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Ki-67 Antigen - analysis</subject><subject>Laboratory Medicine</subject><subject>London</subject><subject>mediastinum</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MIB-1 cellular proliferation</subject><subject>Morphology</subject><subject>Neoplasm Staging</subject><subject>neuroendocrine carcinoma</subject><subject>Neuroendocrine tumors</subject><subject>Neuroendocrine Tumors - chemistry</subject><subject>Neuroendocrine Tumors - immunology</subject><subject>Neuroendocrine Tumors - mortality</subject><subject>Neuroendocrine Tumors - pathology</subject><subject>Neuroendocrine Tumors - therapy</subject><subject>Odds Ratio</subject><subject>original-article</subject><subject>p53</subject><subject>Pathology</subject><subject>Proto-Oncogene Proteins c-bcl-2 - analysis</subject><subject>Risk Assessment</subject><subject>thymus</subject><subject>Thymus gland</subject><subject>Thymus Neoplasms - chemistry</subject><subject>Thymus Neoplasms - immunology</subject><subject>Thymus Neoplasms - mortality</subject><subject>Thymus Neoplasms - pathology</subject><subject>Thymus Neoplasms - therapy</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</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>eNp9kL1OHDEUhS0UxG4WHiBFIitFqh3w7_yIKkJJQEKigYbG8njuZI1m7InticTbx6tZsVIK3Lg4536-_hD6RMklJby-Gn036bTzwyWvST7NCVpTyUlBWC0_oDWpG17wRrIV-hjjCyFUyJqdoRUVJae84mv0PEm-xQaGYR50wFPwg-0h6GS922LtOqwnPyUfbSwCDDpBh3ttkg8RW4fT7nW0BjuYgwfXeROsA5zmMefn6LTXQ4SLw71BTz9_PN7cFvcPv-5uvt8XRkqSCsZLQVktZFUzWnGoaiLKspFCG0IYEUx2FW0FaXlfllXDNLSa0JL3zPRtX3G-Qd8Wbl7-zwwxqdHG_Y-0Az9HldVUTSlELn79r_ji5-DybooxyrKcrGWD6FIywccYoFdTsKMOr4oStbeu3qyrg_U88-UAntsRuuPEQXMusKUQc-R-Qzi-_B718zLkdJoDvFGP-fWSQ5b712ZoNBacgc4GMEl13r5D_wfDZa5Q</recordid><startdate>20040101</startdate><enddate>20040101</enddate><creator>Gal, Anthony A</creator><creator>Sheppard, Mary N</creator><creator>Nolen, John D L</creator><creator>Cohen, Cynthia</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>20040101</creationdate><title>p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors</title><author>Gal, Anthony A ; Sheppard, Mary N ; Nolen, John D L ; Cohen, Cynthia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-236412845782173e780466954ac0020425d71b40b3f66792aeba0163f2cfbf733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - analysis</topic><topic>Bax</topic><topic>Bcl-2</topic><topic>bcl-2-Associated X Protein - analysis</topic><topic>Bcl-x</topic><topic>bcl-X Protein - analysis</topic><topic>carcinoid tumor</topic><topic>Cell Proliferation</topic><topic>Enzymes</topic><topic>Follow-Up Studies</topic><topic>Georgia</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Ki-67 Antigen - analysis</topic><topic>Laboratory Medicine</topic><topic>London</topic><topic>mediastinum</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>MIB-1 cellular proliferation</topic><topic>Morphology</topic><topic>Neoplasm Staging</topic><topic>neuroendocrine carcinoma</topic><topic>Neuroendocrine tumors</topic><topic>Neuroendocrine Tumors - chemistry</topic><topic>Neuroendocrine Tumors - immunology</topic><topic>Neuroendocrine Tumors - mortality</topic><topic>Neuroendocrine Tumors - pathology</topic><topic>Neuroendocrine Tumors - therapy</topic><topic>Odds Ratio</topic><topic>original-article</topic><topic>p53</topic><topic>Pathology</topic><topic>Proto-Oncogene Proteins c-bcl-2 - analysis</topic><topic>Risk Assessment</topic><topic>thymus</topic><topic>Thymus gland</topic><topic>Thymus Neoplasms - chemistry</topic><topic>Thymus Neoplasms - immunology</topic><topic>Thymus Neoplasms - mortality</topic><topic>Thymus Neoplasms - pathology</topic><topic>Thymus Neoplasms - therapy</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gal, Anthony A</creatorcontrib><creatorcontrib>Sheppard, Mary N</creatorcontrib><creatorcontrib>Nolen, John D L</creatorcontrib><creatorcontrib>Cohen, Cynthia</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>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>MEDLINE - Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gal, Anthony A</au><au>Sheppard, Mary N</au><au>Nolen, John D L</au><au>Cohen, Cynthia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2004-01-01</date><risdate>2004</risdate><volume>17</volume><issue>1</issue><spage>33</spage><epage>39</epage><pages>33-39</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2–12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2–15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2–80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (P<0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity × percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (P<0.05). Finally, a Bcl-x : Bax ratio ≥1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio ≥1 (P<0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>14631373</pmid><doi>10.1038/modpathol.3800009</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Apoptosis Apoptosis Regulatory Proteins - analysis Bax Bcl-2 bcl-2-Associated X Protein - analysis Bcl-x bcl-X Protein - analysis carcinoid tumor Cell Proliferation Enzymes Follow-Up Studies Georgia Humans Kaplan-Meier Estimate Ki-67 Antigen - analysis Laboratory Medicine London mediastinum Medicine Medicine & Public Health MIB-1 cellular proliferation Morphology Neoplasm Staging neuroendocrine carcinoma Neuroendocrine tumors Neuroendocrine Tumors - chemistry Neuroendocrine Tumors - immunology Neuroendocrine Tumors - mortality Neuroendocrine Tumors - pathology Neuroendocrine Tumors - therapy Odds Ratio original-article p53 Pathology Proto-Oncogene Proteins c-bcl-2 - analysis Risk Assessment thymus Thymus gland Thymus Neoplasms - chemistry Thymus Neoplasms - immunology Thymus Neoplasms - mortality Thymus Neoplasms - pathology Thymus Neoplasms - therapy Time Factors Treatment Outcome Tumor Suppressor Protein p53 - analysis |
| title | p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors |
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