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Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases
BackgroundTumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (...
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| Published in: | Journal for immunotherapy of cancer 2016-11, Vol.4 (1), p.78-78, Article 78 |
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| container_end_page | 78 |
| container_issue | 1 |
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| container_title | Journal for immunotherapy of cancer |
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| creator | Ferns, Debbie M. Heeren, A. Marijne Samuels, Sanne Bleeker, Maaike C. G. de Gruijl, Tanja D. Kenter, Gemma G. Jordanova, Ekaterina S. |
| description | BackgroundTumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort.MethodsClassical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry. The Chi2 test was used for the comparison of clinicopathological characteristics between SCC and AC patients. The Related-Samples Wilcoxon Signed Rank test was used to compare HLA expression between the primary tumor and metastasis in LN. Patient survival rates were analyzed by Kaplan-Meier curves and Log Rank test. The Mann-Whitney U Test was used to compare the distribution of HLA class I expression between SCC and AC.ResultsDecreased expression of HLA-A (SCC P |
| doi_str_mv | 10.1186/s40425-016-0184-3 |
| format | article |
| fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_09b2f246652646ba8f3a8dc9b5326634</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A470252976</galeid><doaj_id>oai_doaj_org_article_09b2f246652646ba8f3a8dc9b5326634</doaj_id><sourcerecordid>A470252976</sourcerecordid><originalsourceid>FETCH-LOGICAL-b629t-cfe5740f0803bd66ad80376121dbca315189bcb967c549249ab5bff08ec06143</originalsourceid><addsrcrecordid>eNp1kt9q2zAUxs3YWEvWB9jNMAzGbtzpn2X5ZhDC1gYCu-m9OJLlRMGWUsku9AX23FOcLE1Gh2UsHf_OdzhHX5Z9xOgWY8G_RYYYKQuEeXoFK-ib7JqgEheYEf72bH-V3cS4RQhhRKkQ4n12RSpRlzUW19nvRQcxWg1dDq7JnXeFPkXuV_N8OuXLHJQJAQbrXcyty3fB9hCec23C08TGxxF6P8Zi0oHGOK8haOt8D3GK7cAG0-Tdc7_bpEKNyXszQEzLxA_Zuxa6aG6O31n28PPHw-K-WP26Wy7mq0JxUg-Fbk1ZMdQigahqOIcmbSqOCW6UBopLLGqlVc0rXbKasBpUqdqEG404ZnSWLQ-yjYetPPYgPVg5BXxYSwiD1Z2RqFakJYzzknDGFYiWgmh0rUpKOKd7re8Hrd2oetNo44YA3YXo5R9nN3Ltn2SJUV0liVn29SgQ_ONo4iB7G7XpOnAmDVKmS2Uc7W8qoZ__Qbd-DC5NShJORfKDqMQLtYbUgHWtT3X1XlTOWYVISVLdRN2-QqWnMb3V3pnWpvhFwpezhI2BbthE342TFy5BfAB18DEG056GgZHce1YePCuTZ-Xes5KmnE_nUzxl_HVoAooDoPrtS9f_F_wDnEzzPw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2638118878</pqid></control><display><type>article</type><title>Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases</title><source>BMJ Open Access Journals</source><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Ferns, Debbie M. ; Heeren, A. Marijne ; Samuels, Sanne ; Bleeker, Maaike C. G. ; de Gruijl, Tanja D. ; Kenter, Gemma G. ; Jordanova, Ekaterina S.</creator><creatorcontrib>Ferns, Debbie M. ; Heeren, A. Marijne ; Samuels, Sanne ; Bleeker, Maaike C. G. ; de Gruijl, Tanja D. ; Kenter, Gemma G. ; Jordanova, Ekaterina S.</creatorcontrib><description>BackgroundTumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort.MethodsClassical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry. The Chi2 test was used for the comparison of clinicopathological characteristics between SCC and AC patients. The Related-Samples Wilcoxon Signed Rank test was used to compare HLA expression between the primary tumor and metastasis in LN. Patient survival rates were analyzed by Kaplan-Meier curves and Log Rank test. The Mann-Whitney U Test was used to compare the distribution of HLA class I expression between SCC and AC.ResultsDecreased expression of HLA-A (SCC P < 0.001), HLA-B/C (SCC P < 0.01; AC P < 0.01) and total classical HLA (SCC P < 0.001; AC P = 0.02) was apparent in metastatic tumor cells compared to the primary tumor. In primary SCC, there was a clear trend towards complete loss of HLA-A (P = 0.05). SCC metastases showed more complete loss of HLA-A, while AC metastases showed more complete loss of HLA-B/C (P = 0.04). In addition, tumor size and parametrium involvement were also related to aberrant HLA class I expression. No significant associations between HLA expression and disease-specific (DSS) or disease-free survival (DFS) were found in this advanced disease cohort. However, in the SCC group, samples showing loss of HLA-A or loss of total classical HLA but positive for HLA-G were linked to poor patient survival (DSS P = 0.001 and P = 0.01; DFS P = 0.003 and P = 0.01, for HLA-A and total classical HLA, respectively).ConclusionThese results strengthen the idea of tumor immune escape variants leading to metastasis. Moreover, SCC tumors showing downregulation of HLA-A or total classical HLA in combination with HLA-G expression had poor prognosis. Our findings warrant further analysis of HLA expression as a biomarker for patient selection for CTL- and NK- cell based immunotherapeutic intervention.</description><identifier>ISSN: 2051-1426</identifier><identifier>EISSN: 2051-1426</identifier><identifier>DOI: 10.1186/s40425-016-0184-3</identifier><identifier>PMID: 27895918</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Analysis ; Antigens ; Biomarkers ; Cancer ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - mortality ; Care and treatment ; Cervical cancer ; Chemotherapy ; Classical and non-classical HLA expression ; Development and progression ; Diagnosis ; Female ; Gene Expression ; Genetic Variation ; Gynecology ; Health aspects ; Histocompatibility antigens ; Histocompatibility Antigens Class I - genetics ; HLA histocompatibility antigens ; Human papillomavirus ; Humans ; Immune system ; Immunohistochemistry ; Immunotherapy ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Metastasis ; Metastatic lymph nodes ; Middle Aged ; Neoplasm Staging ; Pathology ; Patients ; Primary tumor ; Prognosis ; Research Article ; Squamous cell carcinoma ; Survival analysis ; Tumor Burden ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - mortality ; Uterine Cervical Neoplasms - pathology ; Young Adult</subject><ispartof>Journal for immunotherapy of cancer, 2016-11, Vol.4 (1), p.78-78, Article 78</ispartof><rights>© The Author(s). 2016</rights><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b629t-cfe5740f0803bd66ad80376121dbca315189bcb967c549249ab5bff08ec06143</citedby><cites>FETCH-LOGICAL-b629t-cfe5740f0803bd66ad80376121dbca315189bcb967c549249ab5bff08ec06143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2638118878/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2638118878?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,55350,75126,77660,77686</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27895918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferns, Debbie M.</creatorcontrib><creatorcontrib>Heeren, A. Marijne</creatorcontrib><creatorcontrib>Samuels, Sanne</creatorcontrib><creatorcontrib>Bleeker, Maaike C. G.</creatorcontrib><creatorcontrib>de Gruijl, Tanja D.</creatorcontrib><creatorcontrib>Kenter, Gemma G.</creatorcontrib><creatorcontrib>Jordanova, Ekaterina S.</creatorcontrib><title>Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases</title><title>Journal for immunotherapy of cancer</title><addtitle>J Immunother Cancer</addtitle><addtitle>J Immunother Cancer</addtitle><description>BackgroundTumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort.MethodsClassical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry. The Chi2 test was used for the comparison of clinicopathological characteristics between SCC and AC patients. The Related-Samples Wilcoxon Signed Rank test was used to compare HLA expression between the primary tumor and metastasis in LN. Patient survival rates were analyzed by Kaplan-Meier curves and Log Rank test. The Mann-Whitney U Test was used to compare the distribution of HLA class I expression between SCC and AC.ResultsDecreased expression of HLA-A (SCC P < 0.001), HLA-B/C (SCC P < 0.01; AC P < 0.01) and total classical HLA (SCC P < 0.001; AC P = 0.02) was apparent in metastatic tumor cells compared to the primary tumor. In primary SCC, there was a clear trend towards complete loss of HLA-A (P = 0.05). SCC metastases showed more complete loss of HLA-A, while AC metastases showed more complete loss of HLA-B/C (P = 0.04). In addition, tumor size and parametrium involvement were also related to aberrant HLA class I expression. No significant associations between HLA expression and disease-specific (DSS) or disease-free survival (DFS) were found in this advanced disease cohort. However, in the SCC group, samples showing loss of HLA-A or loss of total classical HLA but positive for HLA-G were linked to poor patient survival (DSS P = 0.001 and P = 0.01; DFS P = 0.003 and P = 0.01, for HLA-A and total classical HLA, respectively).ConclusionThese results strengthen the idea of tumor immune escape variants leading to metastasis. Moreover, SCC tumors showing downregulation of HLA-A or total classical HLA in combination with HLA-G expression had poor prognosis. Our findings warrant further analysis of HLA expression as a biomarker for patient selection for CTL- and NK- cell based immunotherapeutic intervention.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Analysis</subject><subject>Antigens</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Care and treatment</subject><subject>Cervical cancer</subject><subject>Chemotherapy</subject><subject>Classical and non-classical HLA expression</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Genetic Variation</subject><subject>Gynecology</subject><subject>Health aspects</subject><subject>Histocompatibility antigens</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>HLA histocompatibility antigens</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphatic Metastasis</subject><subject>Metastasis</subject><subject>Metastatic lymph nodes</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Pathology</subject><subject>Patients</subject><subject>Primary tumor</subject><subject>Prognosis</subject><subject>Research Article</subject><subject>Squamous cell carcinoma</subject><subject>Survival analysis</subject><subject>Tumor Burden</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Cervical Neoplasms - mortality</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Young Adult</subject><issn>2051-1426</issn><issn>2051-1426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kt9q2zAUxs3YWEvWB9jNMAzGbtzpn2X5ZhDC1gYCu-m9OJLlRMGWUsku9AX23FOcLE1Gh2UsHf_OdzhHX5Z9xOgWY8G_RYYYKQuEeXoFK-ib7JqgEheYEf72bH-V3cS4RQhhRKkQ4n12RSpRlzUW19nvRQcxWg1dDq7JnXeFPkXuV_N8OuXLHJQJAQbrXcyty3fB9hCec23C08TGxxF6P8Zi0oHGOK8haOt8D3GK7cAG0-Tdc7_bpEKNyXszQEzLxA_Zuxa6aG6O31n28PPHw-K-WP26Wy7mq0JxUg-Fbk1ZMdQigahqOIcmbSqOCW6UBopLLGqlVc0rXbKasBpUqdqEG404ZnSWLQ-yjYetPPYgPVg5BXxYSwiD1Z2RqFakJYzzknDGFYiWgmh0rUpKOKd7re8Hrd2oetNo44YA3YXo5R9nN3Ltn2SJUV0liVn29SgQ_ONo4iB7G7XpOnAmDVKmS2Uc7W8qoZ__Qbd-DC5NShJORfKDqMQLtYbUgHWtT3X1XlTOWYVISVLdRN2-QqWnMb3V3pnWpvhFwpezhI2BbthE342TFy5BfAB18DEG056GgZHce1YePCuTZ-Xes5KmnE_nUzxl_HVoAooDoPrtS9f_F_wDnEzzPw</recordid><startdate>20161115</startdate><enddate>20161115</enddate><creator>Ferns, Debbie M.</creator><creator>Heeren, A. Marijne</creator><creator>Samuels, Sanne</creator><creator>Bleeker, Maaike C. G.</creator><creator>de Gruijl, Tanja D.</creator><creator>Kenter, Gemma G.</creator><creator>Jordanova, Ekaterina S.</creator><general>BMJ Publishing Group Ltd</general><general>BioMed Central Ltd</general><general>BMJ Publishing Group LTD</general><general>BioMed Central</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20161115</creationdate><title>Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases</title><author>Ferns, Debbie M. ; Heeren, A. Marijne ; Samuels, Sanne ; Bleeker, Maaike C. G. ; de Gruijl, Tanja D. ; Kenter, Gemma G. ; Jordanova, Ekaterina S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b629t-cfe5740f0803bd66ad80376121dbca315189bcb967c549249ab5bff08ec06143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Analysis</topic><topic>Antigens</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - mortality</topic><topic>Care and treatment</topic><topic>Cervical cancer</topic><topic>Chemotherapy</topic><topic>Classical and non-classical HLA expression</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Genetic Variation</topic><topic>Gynecology</topic><topic>Health aspects</topic><topic>Histocompatibility antigens</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>HLA histocompatibility antigens</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymphatic Metastasis</topic><topic>Metastasis</topic><topic>Metastatic lymph nodes</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Pathology</topic><topic>Patients</topic><topic>Primary tumor</topic><topic>Prognosis</topic><topic>Research Article</topic><topic>Squamous cell carcinoma</topic><topic>Survival analysis</topic><topic>Tumor Burden</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Cervical Neoplasms - mortality</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferns, Debbie M.</creatorcontrib><creatorcontrib>Heeren, A. Marijne</creatorcontrib><creatorcontrib>Samuels, Sanne</creatorcontrib><creatorcontrib>Bleeker, Maaike C. G.</creatorcontrib><creatorcontrib>de Gruijl, Tanja D.</creatorcontrib><creatorcontrib>Kenter, Gemma G.</creatorcontrib><creatorcontrib>Jordanova, Ekaterina S.</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals: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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Journal for immunotherapy of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferns, Debbie M.</au><au>Heeren, A. Marijne</au><au>Samuels, Sanne</au><au>Bleeker, Maaike C. G.</au><au>de Gruijl, Tanja D.</au><au>Kenter, Gemma G.</au><au>Jordanova, Ekaterina S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases</atitle><jtitle>Journal for immunotherapy of cancer</jtitle><stitle>J Immunother Cancer</stitle><addtitle>J Immunother Cancer</addtitle><date>2016-11-15</date><risdate>2016</risdate><volume>4</volume><issue>1</issue><spage>78</spage><epage>78</epage><pages>78-78</pages><artnum>78</artnum><issn>2051-1426</issn><eissn>2051-1426</eissn><abstract>BackgroundTumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort.MethodsClassical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry. The Chi2 test was used for the comparison of clinicopathological characteristics between SCC and AC patients. The Related-Samples Wilcoxon Signed Rank test was used to compare HLA expression between the primary tumor and metastasis in LN. Patient survival rates were analyzed by Kaplan-Meier curves and Log Rank test. The Mann-Whitney U Test was used to compare the distribution of HLA class I expression between SCC and AC.ResultsDecreased expression of HLA-A (SCC P < 0.001), HLA-B/C (SCC P < 0.01; AC P < 0.01) and total classical HLA (SCC P < 0.001; AC P = 0.02) was apparent in metastatic tumor cells compared to the primary tumor. In primary SCC, there was a clear trend towards complete loss of HLA-A (P = 0.05). SCC metastases showed more complete loss of HLA-A, while AC metastases showed more complete loss of HLA-B/C (P = 0.04). In addition, tumor size and parametrium involvement were also related to aberrant HLA class I expression. No significant associations between HLA expression and disease-specific (DSS) or disease-free survival (DFS) were found in this advanced disease cohort. However, in the SCC group, samples showing loss of HLA-A or loss of total classical HLA but positive for HLA-G were linked to poor patient survival (DSS P = 0.001 and P = 0.01; DFS P = 0.003 and P = 0.01, for HLA-A and total classical HLA, respectively).ConclusionThese results strengthen the idea of tumor immune escape variants leading to metastasis. Moreover, SCC tumors showing downregulation of HLA-A or total classical HLA in combination with HLA-G expression had poor prognosis. Our findings warrant further analysis of HLA expression as a biomarker for patient selection for CTL- and NK- cell based immunotherapeutic intervention.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd</pub><pmid>27895918</pmid><doi>10.1186/s40425-016-0184-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - mortality Adenocarcinoma - pathology Adult Aged Aged, 80 and over Alleles Analysis Antigens Biomarkers Cancer Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - mortality Care and treatment Cervical cancer Chemotherapy Classical and non-classical HLA expression Development and progression Diagnosis Female Gene Expression Genetic Variation Gynecology Health aspects Histocompatibility antigens Histocompatibility Antigens Class I - genetics HLA histocompatibility antigens Human papillomavirus Humans Immune system Immunohistochemistry Immunotherapy Kaplan-Meier Estimate Lymphatic Metastasis Metastasis Metastatic lymph nodes Middle Aged Neoplasm Staging Pathology Patients Primary tumor Prognosis Research Article Squamous cell carcinoma Survival analysis Tumor Burden Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - mortality Uterine Cervical Neoplasms - pathology Young Adult |
| title | Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T15%3A19%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Classical%20and%20non-classical%20HLA%20class%20I%20aberrations%20in%20primary%20cervical%20squamous-%20and%20adenocarcinomas%20and%20paired%20lymph%20node%20metastases&rft.jtitle=Journal%20for%20immunotherapy%20of%20cancer&rft.au=Ferns,%20Debbie%20M.&rft.date=2016-11-15&rft.volume=4&rft.issue=1&rft.spage=78&rft.epage=78&rft.pages=78-78&rft.artnum=78&rft.issn=2051-1426&rft.eissn=2051-1426&rft_id=info:doi/10.1186/s40425-016-0184-3&rft_dat=%3Cgale_doaj_%3EA470252976%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-b629t-cfe5740f0803bd66ad80376121dbca315189bcb967c549249ab5bff08ec06143%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2638118878&rft_id=info:pmid/27895918&rft_galeid=A470252976&rfr_iscdi=true |