RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma
Background The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high...
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| Veröffentlicht in: | Pediatric blood & cancer 2011-05, Vol.56 (5), p.738-743 |
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| creator | Lee, Jun Ah Jung, Jun Soo Kim, Dong Ho Lim, Jung Sub Kim, Min Suk Kong, Chang-Bae Song, Won Seok Cho, Wan Hyeong Jeon, Dae-Geun Lee, Soo-Yong Koh, Jae-Soo |
| description | Background
The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high‐grade osteosarcoma.
Patients and methods
This retrospective, immunohistochemical study was performed using materials obtained from 40 patients treated at Korea Cancer Center Hospital between 1995 and 2007. Prechemotherapy biopsy samples were stained for RANKL and correlations between RANKL expression and clinical characteristics and outcomes were evaluated. Staining was interpreted in a semiquantitative manner using an intensity based scoring system.
Results
Thirty cases (75.0%) stained positively for RANKL; 15 (50.0%) had a high RANKL score (≥ 4) and the other 15 a low RANKL score (≤3). RANKL expression and RANKL scores were not related to age, sex, tumor location, tumor volume, or pathologic subtype. However, RANKL expression was related to a poor response to preoperative chemotherapy (P = 0.03) and a high RANKL score was associated with inferior survival. The 5‐year event‐free survival of patients with RANKL score ≥4 was 17.8 ± 10.5%, which was far worse than those with RANKL scores 1–3 or 0 (50.0 ± 15.8%, 56.0 ± 13.7%, respectively, P = 0.02).
Conclusions
The RANKL–RANK–OPG axis might be a promising target for the treatment of osteosarcoma, but further studies are needed to verify our data in a larger cohort. Pediatr Blood Cancer 2011;56:738–743. © 2010 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/pbc.22720 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_855201736</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>855201736</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3620-81b0a61eab34fb8dfd759a689e62c80693ddede4ad8e99edafe1f03ed0af135b3</originalsourceid><addsrcrecordid>eNp1kEFP2zAYhq0JNBjbgT-AfENIC9hx7SRHWm0MqGCgjR2tL_EXakjqzHZFu1-PodDbTv5kPe9zeAjZ5-yYM5afDHVznOdFzj6QXS5HMpOMF1ubm1U75FMIDwlVTJYfyU7ORcFGTO4Sc3t6dTmluBw8hmDdnNpAPXYQ0dDoaPQIscd5pG4RG9cjdS0dINr0FeiTjTPauQY6-w_NVzqz97Ps3oNJWIjoAvi0gc9ku4Uu4Je3d4_8_v7t1-RHNr0-O5-cTrNGqJxlJa8ZKI5Qi1Fbl6Y1haxAlRWqvCmZqoQxaHAEpsSqQgMt8pYJNAxaLmQt9sjh2jt493eBIerehga7DuboFkGXUuapjFCJPFqTjXcheGz14G0PfqU50y9NdWqqX5sm9uDNuqh7NBvyPWICTtbAk-1w9X-T_jmevCuz9cKmSsvNAvyjVoUopP5zdaYvxpO76Y1Q-k48A1vMkYA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>855201736</pqid></control><display><type>article</type><title>RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Lee, Jun Ah ; Jung, Jun Soo ; Kim, Dong Ho ; Lim, Jung Sub ; Kim, Min Suk ; Kong, Chang-Bae ; Song, Won Seok ; Cho, Wan Hyeong ; Jeon, Dae-Geun ; Lee, Soo-Yong ; Koh, Jae-Soo</creator><creatorcontrib>Lee, Jun Ah ; Jung, Jun Soo ; Kim, Dong Ho ; Lim, Jung Sub ; Kim, Min Suk ; Kong, Chang-Bae ; Song, Won Seok ; Cho, Wan Hyeong ; Jeon, Dae-Geun ; Lee, Soo-Yong ; Koh, Jae-Soo</creatorcontrib><description>Background
The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high‐grade osteosarcoma.
Patients and methods
This retrospective, immunohistochemical study was performed using materials obtained from 40 patients treated at Korea Cancer Center Hospital between 1995 and 2007. Prechemotherapy biopsy samples were stained for RANKL and correlations between RANKL expression and clinical characteristics and outcomes were evaluated. Staining was interpreted in a semiquantitative manner using an intensity based scoring system.
Results
Thirty cases (75.0%) stained positively for RANKL; 15 (50.0%) had a high RANKL score (≥ 4) and the other 15 a low RANKL score (≤3). RANKL expression and RANKL scores were not related to age, sex, tumor location, tumor volume, or pathologic subtype. However, RANKL expression was related to a poor response to preoperative chemotherapy (P = 0.03) and a high RANKL score was associated with inferior survival. The 5‐year event‐free survival of patients with RANKL score ≥4 was 17.8 ± 10.5%, which was far worse than those with RANKL scores 1–3 or 0 (50.0 ± 15.8%, 56.0 ± 13.7%, respectively, P = 0.02).
Conclusions
The RANKL–RANK–OPG axis might be a promising target for the treatment of osteosarcoma, but further studies are needed to verify our data in a larger cohort. Pediatr Blood Cancer 2011;56:738–743. © 2010 Wiley‐Liss, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.22720</identifier><identifier>PMID: 21370405</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor - metabolism ; Bone Neoplasms - metabolism ; Bone Neoplasms - pathology ; Bone Neoplasms - therapy ; Child ; Child, Preschool ; Female ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Staging ; osteosarcoma ; Osteosarcoma - metabolism ; Osteosarcoma - pathology ; Osteosarcoma - therapy ; Prognosis ; RANK Ligand - metabolism ; RANKL ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult</subject><ispartof>Pediatric blood & cancer, 2011-05, Vol.56 (5), p.738-743</ispartof><rights>Copyright © 2011 Wiley‐Liss, Inc.</rights><rights>Copyright © 2011 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3620-81b0a61eab34fb8dfd759a689e62c80693ddede4ad8e99edafe1f03ed0af135b3</citedby><cites>FETCH-LOGICAL-c3620-81b0a61eab34fb8dfd759a689e62c80693ddede4ad8e99edafe1f03ed0af135b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.22720$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.22720$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21370405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jun Ah</creatorcontrib><creatorcontrib>Jung, Jun Soo</creatorcontrib><creatorcontrib>Kim, Dong Ho</creatorcontrib><creatorcontrib>Lim, Jung Sub</creatorcontrib><creatorcontrib>Kim, Min Suk</creatorcontrib><creatorcontrib>Kong, Chang-Bae</creatorcontrib><creatorcontrib>Song, Won Seok</creatorcontrib><creatorcontrib>Cho, Wan Hyeong</creatorcontrib><creatorcontrib>Jeon, Dae-Geun</creatorcontrib><creatorcontrib>Lee, Soo-Yong</creatorcontrib><creatorcontrib>Koh, Jae-Soo</creatorcontrib><title>RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma</title><title>Pediatric blood & cancer</title><addtitle>Pediatr. Blood Cancer</addtitle><description>Background
The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high‐grade osteosarcoma.
Patients and methods
This retrospective, immunohistochemical study was performed using materials obtained from 40 patients treated at Korea Cancer Center Hospital between 1995 and 2007. Prechemotherapy biopsy samples were stained for RANKL and correlations between RANKL expression and clinical characteristics and outcomes were evaluated. Staining was interpreted in a semiquantitative manner using an intensity based scoring system.
Results
Thirty cases (75.0%) stained positively for RANKL; 15 (50.0%) had a high RANKL score (≥ 4) and the other 15 a low RANKL score (≤3). RANKL expression and RANKL scores were not related to age, sex, tumor location, tumor volume, or pathologic subtype. However, RANKL expression was related to a poor response to preoperative chemotherapy (P = 0.03) and a high RANKL score was associated with inferior survival. The 5‐year event‐free survival of patients with RANKL score ≥4 was 17.8 ± 10.5%, which was far worse than those with RANKL scores 1–3 or 0 (50.0 ± 15.8%, 56.0 ± 13.7%, respectively, P = 0.02).
Conclusions
The RANKL–RANK–OPG axis might be a promising target for the treatment of osteosarcoma, but further studies are needed to verify our data in a larger cohort. Pediatr Blood Cancer 2011;56:738–743. © 2010 Wiley‐Liss, Inc.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - pathology</subject><subject>Bone Neoplasms - therapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>osteosarcoma</subject><subject>Osteosarcoma - metabolism</subject><subject>Osteosarcoma - pathology</subject><subject>Osteosarcoma - therapy</subject><subject>Prognosis</subject><subject>RANK Ligand - metabolism</subject><subject>RANKL</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFP2zAYhq0JNBjbgT-AfENIC9hx7SRHWm0MqGCgjR2tL_EXakjqzHZFu1-PodDbTv5kPe9zeAjZ5-yYM5afDHVznOdFzj6QXS5HMpOMF1ubm1U75FMIDwlVTJYfyU7ORcFGTO4Sc3t6dTmluBw8hmDdnNpAPXYQ0dDoaPQIscd5pG4RG9cjdS0dINr0FeiTjTPauQY6-w_NVzqz97Ps3oNJWIjoAvi0gc9ku4Uu4Je3d4_8_v7t1-RHNr0-O5-cTrNGqJxlJa8ZKI5Qi1Fbl6Y1haxAlRWqvCmZqoQxaHAEpsSqQgMt8pYJNAxaLmQt9sjh2jt493eBIerehga7DuboFkGXUuapjFCJPFqTjXcheGz14G0PfqU50y9NdWqqX5sm9uDNuqh7NBvyPWICTtbAk-1w9X-T_jmevCuz9cKmSsvNAvyjVoUopP5zdaYvxpO76Y1Q-k48A1vMkYA</recordid><startdate>201105</startdate><enddate>201105</enddate><creator>Lee, Jun Ah</creator><creator>Jung, Jun Soo</creator><creator>Kim, Dong Ho</creator><creator>Lim, Jung Sub</creator><creator>Kim, Min Suk</creator><creator>Kong, Chang-Bae</creator><creator>Song, Won Seok</creator><creator>Cho, Wan Hyeong</creator><creator>Jeon, Dae-Geun</creator><creator>Lee, Soo-Yong</creator><creator>Koh, Jae-Soo</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201105</creationdate><title>RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma</title><author>Lee, Jun Ah ; Jung, Jun Soo ; Kim, Dong Ho ; Lim, Jung Sub ; Kim, Min Suk ; Kong, Chang-Bae ; Song, Won Seok ; Cho, Wan Hyeong ; Jeon, Dae-Geun ; Lee, Soo-Yong ; Koh, Jae-Soo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3620-81b0a61eab34fb8dfd759a689e62c80693ddede4ad8e99edafe1f03ed0af135b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Bone Neoplasms - metabolism</topic><topic>Bone Neoplasms - pathology</topic><topic>Bone Neoplasms - therapy</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>osteosarcoma</topic><topic>Osteosarcoma - metabolism</topic><topic>Osteosarcoma - pathology</topic><topic>Osteosarcoma - therapy</topic><topic>Prognosis</topic><topic>RANK Ligand - metabolism</topic><topic>RANKL</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Jun Ah</creatorcontrib><creatorcontrib>Jung, Jun Soo</creatorcontrib><creatorcontrib>Kim, Dong Ho</creatorcontrib><creatorcontrib>Lim, Jung Sub</creatorcontrib><creatorcontrib>Kim, Min Suk</creatorcontrib><creatorcontrib>Kong, Chang-Bae</creatorcontrib><creatorcontrib>Song, Won Seok</creatorcontrib><creatorcontrib>Cho, Wan Hyeong</creatorcontrib><creatorcontrib>Jeon, Dae-Geun</creatorcontrib><creatorcontrib>Lee, Soo-Yong</creatorcontrib><creatorcontrib>Koh, Jae-Soo</creatorcontrib><collection>Istex</collection><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>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Jun Ah</au><au>Jung, Jun Soo</au><au>Kim, Dong Ho</au><au>Lim, Jung Sub</au><au>Kim, Min Suk</au><au>Kong, Chang-Bae</au><au>Song, Won Seok</au><au>Cho, Wan Hyeong</au><au>Jeon, Dae-Geun</au><au>Lee, Soo-Yong</au><au>Koh, Jae-Soo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr. Blood Cancer</addtitle><date>2011-05</date><risdate>2011</risdate><volume>56</volume><issue>5</issue><spage>738</spage><epage>743</epage><pages>738-743</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high‐grade osteosarcoma.
Patients and methods
This retrospective, immunohistochemical study was performed using materials obtained from 40 patients treated at Korea Cancer Center Hospital between 1995 and 2007. Prechemotherapy biopsy samples were stained for RANKL and correlations between RANKL expression and clinical characteristics and outcomes were evaluated. Staining was interpreted in a semiquantitative manner using an intensity based scoring system.
Results
Thirty cases (75.0%) stained positively for RANKL; 15 (50.0%) had a high RANKL score (≥ 4) and the other 15 a low RANKL score (≤3). RANKL expression and RANKL scores were not related to age, sex, tumor location, tumor volume, or pathologic subtype. However, RANKL expression was related to a poor response to preoperative chemotherapy (P = 0.03) and a high RANKL score was associated with inferior survival. The 5‐year event‐free survival of patients with RANKL score ≥4 was 17.8 ± 10.5%, which was far worse than those with RANKL scores 1–3 or 0 (50.0 ± 15.8%, 56.0 ± 13.7%, respectively, P = 0.02).
Conclusions
The RANKL–RANK–OPG axis might be a promising target for the treatment of osteosarcoma, but further studies are needed to verify our data in a larger cohort. Pediatr Blood Cancer 2011;56:738–743. © 2010 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21370405</pmid><doi>10.1002/pbc.22720</doi><tpages>6</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor - metabolism Bone Neoplasms - metabolism Bone Neoplasms - pathology Bone Neoplasms - therapy Child Child, Preschool Female Humans Immunoenzyme Techniques Male Middle Aged Neoplasm Staging osteosarcoma Osteosarcoma - metabolism Osteosarcoma - pathology Osteosarcoma - therapy Prognosis RANK Ligand - metabolism RANKL Retrospective Studies Survival Rate Treatment Outcome Young Adult |
| title | RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma |
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