Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium
Abstract Background High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this...
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| Veröffentlicht in: | European journal of cancer (1990) 2017-07, Vol.79, p.214-225 |
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| creator | Ruscito, Ilary Cacsire Castillo-Tong, Dan Vergote, Ignace Ignat, Iulia Stanske, Mandy Vanderstichele, Adriaan Ganapathi, Ram N Glajzer, Jacek Kulbe, Hagen Trillsch, Fabian Mustea, Alexander Kreuzinger, Caroline Benedetti Panici, Pierluigi Gourley, Charlie Gabra, Hani Kessler, Mirjana Sehouli, Jalid Darb-Esfahani, Silvia Braicu, Elena Ioana |
| description | Abstract Background High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Methods Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Results Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p |
| doi_str_mv | 10.1016/j.ejca.2017.04.016 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1900834215</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0959804917309036</els_id><sourcerecordid>1900834215</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-ad20facbd57ad73c59a4925529d2ec2e87bdf269ce0e6533a0087cdc6bcb14ba3</originalsourceid><addsrcrecordid>eNp9Uk2P0zAQDQjElsIf4IB8bA_J2s63hJCq7LKttKgrtZwtx5607iZxsZOI3vgP_EN-Cc62y4EDp5HG7z3PvHme94HggGCSXB8COAgeUEzSAEeBa730JiRLcx9nMX3lTXAe536Go_zKe2vtAWOcZhF-411R9x5nUTJ5Mb39cay1Ue0OdXtAotYtrxEMuu47pVukK1TckDC85rWE_UmC_1SM3kHLLfgEzRb3N0sy94_aqk4NToO3AgyyHTR-rR5dA-raosroBh2Narg5oU4jA6I3BtoO7dVu7-8Ml4AsGN1bpAduFG-fpWbLu826mAdo4VR7eRqnGqddX2DFGbbdg-HH0--fv1Zt6ySepvmqJbjfH4x2q-3QpjeDGtyKs3WxXT1s5qjQrdWmU33zzntd8drC-0udet--3G6LpX-_vlsVi3tfRHHc-VxSXHFRyjjlMg1FnPMop3FMc0lBUMjSUlY0yQVgSOIw5BhnqZAiKUVJopKHU2921j0a_b0H27FG2dEk3oLbnpHcMcKIkthB6RkqjLbWQMUuDjKC2RgCdmBjCNgYAoYj5lqO9PGi35cNyL-U56s7wKczwDkDgwLDrFDgPJTKXaVjUqv_63_-hy5q1SrB60c4gT3o3rgQuT2YpQyzzRjDMYUkDXGOwyT8A5Y93I8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1900834215</pqid></control><display><type>article</type><title>Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Ruscito, Ilary ; Cacsire Castillo-Tong, Dan ; Vergote, Ignace ; Ignat, Iulia ; Stanske, Mandy ; Vanderstichele, Adriaan ; Ganapathi, Ram N ; Glajzer, Jacek ; Kulbe, Hagen ; Trillsch, Fabian ; Mustea, Alexander ; Kreuzinger, Caroline ; Benedetti Panici, Pierluigi ; Gourley, Charlie ; Gabra, Hani ; Kessler, Mirjana ; Sehouli, Jalid ; Darb-Esfahani, Silvia ; Braicu, Elena Ioana</creator><creatorcontrib>Ruscito, Ilary ; Cacsire Castillo-Tong, Dan ; Vergote, Ignace ; Ignat, Iulia ; Stanske, Mandy ; Vanderstichele, Adriaan ; Ganapathi, Ram N ; Glajzer, Jacek ; Kulbe, Hagen ; Trillsch, Fabian ; Mustea, Alexander ; Kreuzinger, Caroline ; Benedetti Panici, Pierluigi ; Gourley, Charlie ; Gabra, Hani ; Kessler, Mirjana ; Sehouli, Jalid ; Darb-Esfahani, Silvia ; Braicu, Elena Ioana</creatorcontrib><description>Abstract Background High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Methods Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Results Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p < 0.0001). Furthermore, all CD133 + pOC patients were International Federation of Gynaecology and Obstetrics (FIGO)-stage III/IV (p < 0.0001) and had significantly worse progression-free interval (PFI) (p = 0.04) and overall survival (OS) (p = 0.02). On multivariate analysis, CD133/ALDH1 coexpression in pOCs was identified as independent prognostic factor for PFI (HR: 1.64; 95% CI: 1.03–2.60; p = 0.036) and OS (HR: 1.71; 95% CI: 1.01–2.88; p = 0.045). Analysis on 52 pts patients with known somatic BRCA status revealed that BRCA mutations did not influence CSC biomarker expression. Conclusions The study showed that CD133/ALDH1 expression impacts HGSOC patients' survival and first suggests that CSCs might undergo phenotypic change during the disease course similarly to non stem-like cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2017.04.016</identifier><identifier>PMID: 28525846</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>AC133 Antigen - metabolism ; Adult ; Aged ; Aldehyde dehydrogenase-1 ; ALDH1 ; Antineoplastic Agents - therapeutic use ; Biomarkers, Tumor - metabolism ; BRCA ; BRCA2 Protein - metabolism ; Cancer stem-like cell ; Carcinoma, Ovarian Epithelial ; CD133 ; Clonal Evolution ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Isoenzymes - metabolism ; Middle Aged ; Neoplasm Recurrence, Local - enzymology ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - pathology ; Neoplasm, Residual - enzymology ; Neoplasm, Residual - mortality ; Neoplasm, Residual - pathology ; Neoplasms, Glandular and Epithelial - enzymology ; Neoplasms, Glandular and Epithelial - mortality ; Neoplasms, Glandular and Epithelial - pathology ; Neoplastic Stem Cells - enzymology ; Neoplastic Stem Cells - pathology ; Ovarian cancer ; Ovarian Neoplasms - enzymology ; Ovarian Neoplasms - mortality ; Ovarian Neoplasms - pathology ; Platinum Compounds - therapeutic use ; Prognosis ; Retinal Dehydrogenase - metabolism ; Survival ; Survival Analysis ; Ubiquitin-Protein Ligases - metabolism</subject><ispartof>European journal of cancer (1990), 2017-07, Vol.79, p.214-225</ispartof><rights>Elsevier Ltd</rights><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-ad20facbd57ad73c59a4925529d2ec2e87bdf269ce0e6533a0087cdc6bcb14ba3</citedby><cites>FETCH-LOGICAL-c455t-ad20facbd57ad73c59a4925529d2ec2e87bdf269ce0e6533a0087cdc6bcb14ba3</cites><orcidid>0000-0002-3984-2948</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0959804917309036$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28525846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruscito, Ilary</creatorcontrib><creatorcontrib>Cacsire Castillo-Tong, Dan</creatorcontrib><creatorcontrib>Vergote, Ignace</creatorcontrib><creatorcontrib>Ignat, Iulia</creatorcontrib><creatorcontrib>Stanske, Mandy</creatorcontrib><creatorcontrib>Vanderstichele, Adriaan</creatorcontrib><creatorcontrib>Ganapathi, Ram N</creatorcontrib><creatorcontrib>Glajzer, Jacek</creatorcontrib><creatorcontrib>Kulbe, Hagen</creatorcontrib><creatorcontrib>Trillsch, Fabian</creatorcontrib><creatorcontrib>Mustea, Alexander</creatorcontrib><creatorcontrib>Kreuzinger, Caroline</creatorcontrib><creatorcontrib>Benedetti Panici, Pierluigi</creatorcontrib><creatorcontrib>Gourley, Charlie</creatorcontrib><creatorcontrib>Gabra, Hani</creatorcontrib><creatorcontrib>Kessler, Mirjana</creatorcontrib><creatorcontrib>Sehouli, Jalid</creatorcontrib><creatorcontrib>Darb-Esfahani, Silvia</creatorcontrib><creatorcontrib>Braicu, Elena Ioana</creatorcontrib><title>Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Abstract Background High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Methods Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Results Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p < 0.0001). Furthermore, all CD133 + pOC patients were International Federation of Gynaecology and Obstetrics (FIGO)-stage III/IV (p < 0.0001) and had significantly worse progression-free interval (PFI) (p = 0.04) and overall survival (OS) (p = 0.02). On multivariate analysis, CD133/ALDH1 coexpression in pOCs was identified as independent prognostic factor for PFI (HR: 1.64; 95% CI: 1.03–2.60; p = 0.036) and OS (HR: 1.71; 95% CI: 1.01–2.88; p = 0.045). Analysis on 52 pts patients with known somatic BRCA status revealed that BRCA mutations did not influence CSC biomarker expression. Conclusions The study showed that CD133/ALDH1 expression impacts HGSOC patients' survival and first suggests that CSCs might undergo phenotypic change during the disease course similarly to non stem-like cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status.</description><subject>AC133 Antigen - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>Aldehyde dehydrogenase-1</subject><subject>ALDH1</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>BRCA</subject><subject>BRCA2 Protein - metabolism</subject><subject>Cancer stem-like cell</subject><subject>Carcinoma, Ovarian Epithelial</subject><subject>CD133</subject><subject>Clonal Evolution</subject><subject>Female</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Isoenzymes - metabolism</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - enzymology</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm, Residual - enzymology</subject><subject>Neoplasm, Residual - mortality</subject><subject>Neoplasm, Residual - pathology</subject><subject>Neoplasms, Glandular and Epithelial - enzymology</subject><subject>Neoplasms, Glandular and Epithelial - mortality</subject><subject>Neoplasms, Glandular and Epithelial - pathology</subject><subject>Neoplastic Stem Cells - enzymology</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - enzymology</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Platinum Compounds - therapeutic use</subject><subject>Prognosis</subject><subject>Retinal Dehydrogenase - metabolism</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uk2P0zAQDQjElsIf4IB8bA_J2s63hJCq7LKttKgrtZwtx5607iZxsZOI3vgP_EN-Cc62y4EDp5HG7z3PvHme94HggGCSXB8COAgeUEzSAEeBa730JiRLcx9nMX3lTXAe536Go_zKe2vtAWOcZhF-411R9x5nUTJ5Mb39cay1Ue0OdXtAotYtrxEMuu47pVukK1TckDC85rWE_UmC_1SM3kHLLfgEzRb3N0sy94_aqk4NToO3AgyyHTR-rR5dA-raosroBh2Narg5oU4jA6I3BtoO7dVu7-8Ml4AsGN1bpAduFG-fpWbLu826mAdo4VR7eRqnGqddX2DFGbbdg-HH0--fv1Zt6ySepvmqJbjfH4x2q-3QpjeDGtyKs3WxXT1s5qjQrdWmU33zzntd8drC-0udet--3G6LpX-_vlsVi3tfRHHc-VxSXHFRyjjlMg1FnPMop3FMc0lBUMjSUlY0yQVgSOIw5BhnqZAiKUVJopKHU2921j0a_b0H27FG2dEk3oLbnpHcMcKIkthB6RkqjLbWQMUuDjKC2RgCdmBjCNgYAoYj5lqO9PGi35cNyL-U56s7wKczwDkDgwLDrFDgPJTKXaVjUqv_63_-hy5q1SrB60c4gT3o3rgQuT2YpQyzzRjDMYUkDXGOwyT8A5Y93I8</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Ruscito, Ilary</creator><creator>Cacsire Castillo-Tong, Dan</creator><creator>Vergote, Ignace</creator><creator>Ignat, Iulia</creator><creator>Stanske, Mandy</creator><creator>Vanderstichele, Adriaan</creator><creator>Ganapathi, Ram N</creator><creator>Glajzer, Jacek</creator><creator>Kulbe, Hagen</creator><creator>Trillsch, Fabian</creator><creator>Mustea, Alexander</creator><creator>Kreuzinger, Caroline</creator><creator>Benedetti Panici, Pierluigi</creator><creator>Gourley, Charlie</creator><creator>Gabra, Hani</creator><creator>Kessler, Mirjana</creator><creator>Sehouli, Jalid</creator><creator>Darb-Esfahani, Silvia</creator><creator>Braicu, Elena Ioana</creator><general>Elsevier Ltd</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>7X8</scope><orcidid>https://orcid.org/0000-0002-3984-2948</orcidid></search><sort><creationdate>20170701</creationdate><title>Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium</title><author>Ruscito, Ilary ; Cacsire Castillo-Tong, Dan ; Vergote, Ignace ; Ignat, Iulia ; Stanske, Mandy ; Vanderstichele, Adriaan ; Ganapathi, Ram N ; Glajzer, Jacek ; Kulbe, Hagen ; Trillsch, Fabian ; Mustea, Alexander ; Kreuzinger, Caroline ; Benedetti Panici, Pierluigi ; Gourley, Charlie ; Gabra, Hani ; Kessler, Mirjana ; Sehouli, Jalid ; Darb-Esfahani, Silvia ; Braicu, Elena Ioana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-ad20facbd57ad73c59a4925529d2ec2e87bdf269ce0e6533a0087cdc6bcb14ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>AC133 Antigen - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>Aldehyde dehydrogenase-1</topic><topic>ALDH1</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>BRCA</topic><topic>BRCA2 Protein - metabolism</topic><topic>Cancer stem-like cell</topic><topic>Carcinoma, Ovarian Epithelial</topic><topic>CD133</topic><topic>Clonal Evolution</topic><topic>Female</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Isoenzymes - metabolism</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - enzymology</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Neoplasm, Residual - enzymology</topic><topic>Neoplasm, Residual - mortality</topic><topic>Neoplasm, Residual - pathology</topic><topic>Neoplasms, Glandular and Epithelial - enzymology</topic><topic>Neoplasms, Glandular and Epithelial - mortality</topic><topic>Neoplasms, Glandular and Epithelial - pathology</topic><topic>Neoplastic Stem Cells - enzymology</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - enzymology</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Platinum Compounds - therapeutic use</topic><topic>Prognosis</topic><topic>Retinal Dehydrogenase - metabolism</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruscito, Ilary</creatorcontrib><creatorcontrib>Cacsire Castillo-Tong, Dan</creatorcontrib><creatorcontrib>Vergote, Ignace</creatorcontrib><creatorcontrib>Ignat, Iulia</creatorcontrib><creatorcontrib>Stanske, Mandy</creatorcontrib><creatorcontrib>Vanderstichele, Adriaan</creatorcontrib><creatorcontrib>Ganapathi, Ram N</creatorcontrib><creatorcontrib>Glajzer, Jacek</creatorcontrib><creatorcontrib>Kulbe, Hagen</creatorcontrib><creatorcontrib>Trillsch, Fabian</creatorcontrib><creatorcontrib>Mustea, Alexander</creatorcontrib><creatorcontrib>Kreuzinger, Caroline</creatorcontrib><creatorcontrib>Benedetti Panici, Pierluigi</creatorcontrib><creatorcontrib>Gourley, Charlie</creatorcontrib><creatorcontrib>Gabra, Hani</creatorcontrib><creatorcontrib>Kessler, Mirjana</creatorcontrib><creatorcontrib>Sehouli, Jalid</creatorcontrib><creatorcontrib>Darb-Esfahani, Silvia</creatorcontrib><creatorcontrib>Braicu, Elena Ioana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ruscito, Ilary</au><au>Cacsire Castillo-Tong, Dan</au><au>Vergote, Ignace</au><au>Ignat, Iulia</au><au>Stanske, Mandy</au><au>Vanderstichele, Adriaan</au><au>Ganapathi, Ram N</au><au>Glajzer, Jacek</au><au>Kulbe, Hagen</au><au>Trillsch, Fabian</au><au>Mustea, Alexander</au><au>Kreuzinger, Caroline</au><au>Benedetti Panici, Pierluigi</au><au>Gourley, Charlie</au><au>Gabra, Hani</au><au>Kessler, Mirjana</au><au>Sehouli, Jalid</au><au>Darb-Esfahani, Silvia</au><au>Braicu, Elena Ioana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>79</volume><spage>214</spage><epage>225</epage><pages>214-225</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Abstract Background High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Methods Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Results Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p < 0.0001). Furthermore, all CD133 + pOC patients were International Federation of Gynaecology and Obstetrics (FIGO)-stage III/IV (p < 0.0001) and had significantly worse progression-free interval (PFI) (p = 0.04) and overall survival (OS) (p = 0.02). On multivariate analysis, CD133/ALDH1 coexpression in pOCs was identified as independent prognostic factor for PFI (HR: 1.64; 95% CI: 1.03–2.60; p = 0.036) and OS (HR: 1.71; 95% CI: 1.01–2.88; p = 0.045). Analysis on 52 pts patients with known somatic BRCA status revealed that BRCA mutations did not influence CSC biomarker expression. Conclusions The study showed that CD133/ALDH1 expression impacts HGSOC patients' survival and first suggests that CSCs might undergo phenotypic change during the disease course similarly to non stem-like cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28525846</pmid><doi>10.1016/j.ejca.2017.04.016</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3984-2948</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of cancer (1990), 2017-07, Vol.79, p.214-225 |
| issn | 0959-8049 1879-0852 |
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| recordid | cdi_proquest_miscellaneous_1900834215 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | AC133 Antigen - metabolism Adult Aged Aldehyde dehydrogenase-1 ALDH1 Antineoplastic Agents - therapeutic use Biomarkers, Tumor - metabolism BRCA BRCA2 Protein - metabolism Cancer stem-like cell Carcinoma, Ovarian Epithelial CD133 Clonal Evolution Female Hematology, Oncology and Palliative Medicine Humans Isoenzymes - metabolism Middle Aged Neoplasm Recurrence, Local - enzymology Neoplasm Recurrence, Local - mortality Neoplasm Recurrence, Local - pathology Neoplasm, Residual - enzymology Neoplasm, Residual - mortality Neoplasm, Residual - pathology Neoplasms, Glandular and Epithelial - enzymology Neoplasms, Glandular and Epithelial - mortality Neoplasms, Glandular and Epithelial - pathology Neoplastic Stem Cells - enzymology Neoplastic Stem Cells - pathology Ovarian cancer Ovarian Neoplasms - enzymology Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Platinum Compounds - therapeutic use Prognosis Retinal Dehydrogenase - metabolism Survival Survival Analysis Ubiquitin-Protein Ligases - metabolism |
| title | Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) Consortium |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T18%3A33%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Exploring%20the%20clonal%20evolution%20of%20CD133/aldehyde-dehydrogenase-1%20(ALDH1)-positive%20cancer%20stem-like%20cells%20from%20primary%20to%20recurrent%20high-grade%20serous%20ovarian%20cancer%20(HGSOC).%20A%20study%20of%20the%20Ovarian%20Cancer%20Therapy%E2%80%93Innovative%20Models%20Prolong%20Survival%20(OCTIPS)%20Consortium&rft.jtitle=European%20journal%20of%20cancer%20(1990)&rft.au=Ruscito,%20Ilary&rft.date=2017-07-01&rft.volume=79&rft.spage=214&rft.epage=225&rft.pages=214-225&rft.issn=0959-8049&rft.eissn=1879-0852&rft_id=info:doi/10.1016/j.ejca.2017.04.016&rft_dat=%3Cproquest_cross%3E1900834215%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1900834215&rft_id=info:pmid/28525846&rft_els_id=1_s2_0_S0959804917309036&rfr_iscdi=true |