Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints
Objective To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. Methods The SEER database was queri...
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| Veröffentlicht in: | Archives of gynecology and obstetrics 2022-02, Vol.305 (2), p.439-447 |
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| creator | Blake, Erin A. Ross, Malcolm S. Ross, Megan E. Matsuo, Koji Silverstein, Emily T. Torno, Lilibeth R. Bhargava, Rohit Post, Miriam D. Da Silva, Diane M. Taylor, Sarah Walia, Saloni Roman, Lynda McEachron, Troy A. |
| description | Objective
To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets.
Methods
The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC.
Results
In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (
p
|
| doi_str_mv | 10.1007/s00404-021-06164-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2561912741</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2561912741</sourcerecordid><originalsourceid>FETCH-LOGICAL-c326t-74b7f94a6c08c425ee4114d40676b834c9b9428340f8597176dc6be2fdbdd48e3</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhS0Eope2L8ACWWLDJtR2HCdZooqfSpXYlHXkOJMbFycOHqe6eaK-Js69LUgsWPnI880Zew4hbzn7yBkrr5AxyWTGBM-Y4kpmhxdkx2UuMlZy_pLsWL1ppsoz8gbxnjEuqkq9Jme5zGuR12pHHm_GcZn8YDF6M8BojXZUT9qtaJH6nu6dRlypAeeo0cHYyY96K8QB0m14sAca4AG0Qxp8u2Ckbh3nwZs1ArVTb10MOkk9dcceOMwBEK2fji467CHq1m3sYFsbfVip3R6V7AcwP2dvp4gX5FWfRsDl03lOfnz5fHf9Lbv9_vXm-tNtZnKhYlbKtuxrqZVhlZGiAJCcy06mHai2yqWp21qKJFhfFXXJS9UZ1YLou7brZAX5Oflw8p2D_7UAxma0uH1eT-AXbESheM1FKXlC3_-D3vslpNUlSomKcVmoIlHiRJngEQP0zRzsqMPacNZsMTanGJsUY3OMsTmkpndP1ks7Qven5Tm3BOQnAFNp2kP4O_s_tr8BSSytGg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2628014565</pqid></control><display><type>article</type><title>Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Blake, Erin A. ; Ross, Malcolm S. ; Ross, Megan E. ; Matsuo, Koji ; Silverstein, Emily T. ; Torno, Lilibeth R. ; Bhargava, Rohit ; Post, Miriam D. ; Da Silva, Diane M. ; Taylor, Sarah ; Walia, Saloni ; Roman, Lynda ; McEachron, Troy A.</creator><creatorcontrib>Blake, Erin A. ; Ross, Malcolm S. ; Ross, Megan E. ; Matsuo, Koji ; Silverstein, Emily T. ; Torno, Lilibeth R. ; Bhargava, Rohit ; Post, Miriam D. ; Da Silva, Diane M. ; Taylor, Sarah ; Walia, Saloni ; Roman, Lynda ; McEachron, Troy A.</creatorcontrib><description>Objective
To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets.
Methods
The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC.
Results
In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (
p
< 0.001) and demonstrated inferior survival (
p
< 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient.
Conclusions
The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.</description><identifier>ISSN: 0932-0067</identifier><identifier>EISSN: 1432-0711</identifier><identifier>DOI: 10.1007/s00404-021-06164-x</identifier><identifier>PMID: 34392396</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>B7-H1 Antigen - metabolism ; Biomarkers, Tumor - metabolism ; Cancer ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell - pathology ; Cervical cancer ; Cervix ; Cervix Uteri - pathology ; Cloning ; Datasets ; Endocrinology ; Epidemiology ; Female ; Gene expression ; Genomics ; Gynecologic Oncology ; Gynecology ; Histology ; Hospitals ; Human Genetics ; Humans ; Laboratories ; Lymphocytes ; Medical prognosis ; Medicine ; Medicine & Public Health ; Metastasis ; Obstetrics ; Obstetrics/Perinatology/Midwifery ; Oncology ; Pathology ; Patients ; Squamous cell carcinoma ; Trends ; Uterine Cervical Neoplasms - pathology</subject><ispartof>Archives of gynecology and obstetrics, 2022-02, Vol.305 (2), p.439-447</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-74b7f94a6c08c425ee4114d40676b834c9b9428340f8597176dc6be2fdbdd48e3</cites><orcidid>0000-0002-5097-4837</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00404-021-06164-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00404-021-06164-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34392396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blake, Erin A.</creatorcontrib><creatorcontrib>Ross, Malcolm S.</creatorcontrib><creatorcontrib>Ross, Megan E.</creatorcontrib><creatorcontrib>Matsuo, Koji</creatorcontrib><creatorcontrib>Silverstein, Emily T.</creatorcontrib><creatorcontrib>Torno, Lilibeth R.</creatorcontrib><creatorcontrib>Bhargava, Rohit</creatorcontrib><creatorcontrib>Post, Miriam D.</creatorcontrib><creatorcontrib>Da Silva, Diane M.</creatorcontrib><creatorcontrib>Taylor, Sarah</creatorcontrib><creatorcontrib>Walia, Saloni</creatorcontrib><creatorcontrib>Roman, Lynda</creatorcontrib><creatorcontrib>McEachron, Troy A.</creatorcontrib><title>Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints</title><title>Archives of gynecology and obstetrics</title><addtitle>Arch Gynecol Obstet</addtitle><addtitle>Arch Gynecol Obstet</addtitle><description>Objective
To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets.
Methods
The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC.
Results
In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (
p
< 0.001) and demonstrated inferior survival (
p
< 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient.
Conclusions
The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.</description><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Carcinoma, Adenosquamous</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cervix Uteri - pathology</subject><subject>Cloning</subject><subject>Datasets</subject><subject>Endocrinology</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Gynecologic Oncology</subject><subject>Gynecology</subject><subject>Histology</subject><subject>Hospitals</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Lymphocytes</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastasis</subject><subject>Obstetrics</subject><subject>Obstetrics/Perinatology/Midwifery</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Patients</subject><subject>Squamous cell carcinoma</subject><subject>Trends</subject><subject>Uterine Cervical Neoplasms - pathology</subject><issn>0932-0067</issn><issn>1432-0711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1u1TAQhS0Eope2L8ACWWLDJtR2HCdZooqfSpXYlHXkOJMbFycOHqe6eaK-Js69LUgsWPnI880Zew4hbzn7yBkrr5AxyWTGBM-Y4kpmhxdkx2UuMlZy_pLsWL1ppsoz8gbxnjEuqkq9Jme5zGuR12pHHm_GcZn8YDF6M8BojXZUT9qtaJH6nu6dRlypAeeo0cHYyY96K8QB0m14sAca4AG0Qxp8u2Ckbh3nwZs1ArVTb10MOkk9dcceOMwBEK2fji467CHq1m3sYFsbfVip3R6V7AcwP2dvp4gX5FWfRsDl03lOfnz5fHf9Lbv9_vXm-tNtZnKhYlbKtuxrqZVhlZGiAJCcy06mHai2yqWp21qKJFhfFXXJS9UZ1YLou7brZAX5Oflw8p2D_7UAxma0uH1eT-AXbESheM1FKXlC3_-D3vslpNUlSomKcVmoIlHiRJngEQP0zRzsqMPacNZsMTanGJsUY3OMsTmkpndP1ks7Qven5Tm3BOQnAFNp2kP4O_s_tr8BSSytGg</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Blake, Erin A.</creator><creator>Ross, Malcolm S.</creator><creator>Ross, Megan E.</creator><creator>Matsuo, Koji</creator><creator>Silverstein, Emily T.</creator><creator>Torno, Lilibeth R.</creator><creator>Bhargava, Rohit</creator><creator>Post, Miriam D.</creator><creator>Da Silva, Diane M.</creator><creator>Taylor, Sarah</creator><creator>Walia, Saloni</creator><creator>Roman, Lynda</creator><creator>McEachron, Troy A.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5097-4837</orcidid></search><sort><creationdate>20220201</creationdate><title>Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints</title><author>Blake, Erin A. ; Ross, Malcolm S. ; Ross, Megan E. ; Matsuo, Koji ; Silverstein, Emily T. ; Torno, Lilibeth R. ; Bhargava, Rohit ; Post, Miriam D. ; Da Silva, Diane M. ; Taylor, Sarah ; Walia, Saloni ; Roman, Lynda ; McEachron, Troy A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-74b7f94a6c08c425ee4114d40676b834c9b9428340f8597176dc6be2fdbdd48e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>B7-H1 Antigen - metabolism</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer</topic><topic>Carcinoma, Adenosquamous</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Cervix Uteri - pathology</topic><topic>Cloning</topic><topic>Datasets</topic><topic>Endocrinology</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genomics</topic><topic>Gynecologic Oncology</topic><topic>Gynecology</topic><topic>Histology</topic><topic>Hospitals</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Laboratories</topic><topic>Lymphocytes</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Obstetrics</topic><topic>Obstetrics/Perinatology/Midwifery</topic><topic>Oncology</topic><topic>Pathology</topic><topic>Patients</topic><topic>Squamous cell carcinoma</topic><topic>Trends</topic><topic>Uterine Cervical Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blake, Erin A.</creatorcontrib><creatorcontrib>Ross, Malcolm S.</creatorcontrib><creatorcontrib>Ross, Megan E.</creatorcontrib><creatorcontrib>Matsuo, Koji</creatorcontrib><creatorcontrib>Silverstein, Emily T.</creatorcontrib><creatorcontrib>Torno, Lilibeth R.</creatorcontrib><creatorcontrib>Bhargava, Rohit</creatorcontrib><creatorcontrib>Post, Miriam D.</creatorcontrib><creatorcontrib>Da Silva, Diane M.</creatorcontrib><creatorcontrib>Taylor, Sarah</creatorcontrib><creatorcontrib>Walia, Saloni</creatorcontrib><creatorcontrib>Roman, Lynda</creatorcontrib><creatorcontrib>McEachron, Troy A.</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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</collection><collection>ProQuest One Community College</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>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>Archives of gynecology and obstetrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blake, Erin A.</au><au>Ross, Malcolm S.</au><au>Ross, Megan E.</au><au>Matsuo, Koji</au><au>Silverstein, Emily T.</au><au>Torno, Lilibeth R.</au><au>Bhargava, Rohit</au><au>Post, Miriam D.</au><au>Da Silva, Diane M.</au><au>Taylor, Sarah</au><au>Walia, Saloni</au><au>Roman, Lynda</au><au>McEachron, Troy A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints</atitle><jtitle>Archives of gynecology and obstetrics</jtitle><stitle>Arch Gynecol Obstet</stitle><addtitle>Arch Gynecol Obstet</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>305</volume><issue>2</issue><spage>439</spage><epage>447</epage><pages>439-447</pages><issn>0932-0067</issn><eissn>1432-0711</eissn><abstract>Objective
To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets.
Methods
The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC.
Results
In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (
p
< 0.001) and demonstrated inferior survival (
p
< 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient.
Conclusions
The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34392396</pmid><doi>10.1007/s00404-021-06164-x</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5097-4837</orcidid></addata></record> |
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| ispartof | Archives of gynecology and obstetrics, 2022-02, Vol.305 (2), p.439-447 |
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| subjects | B7-H1 Antigen - metabolism Biomarkers, Tumor - metabolism Cancer Carcinoma, Adenosquamous Carcinoma, Squamous Cell - pathology Cervical cancer Cervix Cervix Uteri - pathology Cloning Datasets Endocrinology Epidemiology Female Gene expression Genomics Gynecologic Oncology Gynecology Histology Hospitals Human Genetics Humans Laboratories Lymphocytes Medical prognosis Medicine Medicine & Public Health Metastasis Obstetrics Obstetrics/Perinatology/Midwifery Oncology Pathology Patients Squamous cell carcinoma Trends Uterine Cervical Neoplasms - pathology |
| title | Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints |
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