Prospective Comparison of the Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of a Single Patient's Cohort With Esophageal Cancer

OBJECTIVE:Aim of this prospective study was to evaluate the prognostic significance of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) in 1 cohort of patients with esophageal cancer (EC). BACKGROUND:Hematogenous tumor cell dissemination is a key event in tumor progression, and cli...

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Veröffentlicht in:Annals of surgery 2021-02, Vol.273 (2), p.299-305
Hauptverfasser: Konczalla, Leonie, Ghadban, Tarik, Effenberger, Katharina E., Wöstemeier, Anna, Riethdorf, Sabine, Uzunoglu, Faik G., Izbicki, Jakob R., Pantel, Klaus, Bockhorn, Maximilian, Reeh, Matthias
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container_end_page 305
container_issue 2
container_start_page 299
container_title Annals of surgery
container_volume 273
creator Konczalla, Leonie
Ghadban, Tarik
Effenberger, Katharina E.
Wöstemeier, Anna
Riethdorf, Sabine
Uzunoglu, Faik G.
Izbicki, Jakob R.
Pantel, Klaus
Bockhorn, Maximilian
Reeh, Matthias
description OBJECTIVE:Aim of this prospective study was to evaluate the prognostic significance of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) in 1 cohort of patients with esophageal cancer (EC). BACKGROUND:Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patientʼs cohort has not been described before. METHODS:In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3. RESULTS:Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P < 0.001, respectively). CONCLUSIONS:This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.
doi_str_mv 10.1097/SLA.0000000000003406
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BACKGROUND:Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patientʼs cohort has not been described before. METHODS:In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3. RESULTS:Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P &lt; 0.001, respectively). CONCLUSIONS:This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.</description><identifier>ISSN: 0003-4932</identifier><identifier>EISSN: 1528-1140</identifier><identifier>DOI: 10.1097/SLA.0000000000003406</identifier><identifier>PMID: 31188197</identifier><language>eng</language><publisher>United States: Lippincott Williams &amp; Wilkins</publisher><subject>Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Adenocarcinoma - surgery ; Aged ; Bone Marrow - pathology ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - surgery ; Esophageal Neoplasms - mortality ; Esophageal Neoplasms - pathology ; Esophageal Neoplasms - surgery ; Esophagectomy ; Female ; Humans ; Ilium - pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Prognosis ; Prospective Studies ; Survival Rate</subject><ispartof>Annals of surgery, 2021-02, Vol.273 (2), p.299-305</ispartof><rights>Lippincott Williams &amp; Wilkins</rights><rights>Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4016-e496133e1313708f7c1f96d481bb69da40bbe36cf0549e4790009cc7925c85e83</citedby><cites>FETCH-LOGICAL-c4016-e496133e1313708f7c1f96d481bb69da40bbe36cf0549e4790009cc7925c85e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31188197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Konczalla, Leonie</creatorcontrib><creatorcontrib>Ghadban, Tarik</creatorcontrib><creatorcontrib>Effenberger, Katharina E.</creatorcontrib><creatorcontrib>Wöstemeier, Anna</creatorcontrib><creatorcontrib>Riethdorf, Sabine</creatorcontrib><creatorcontrib>Uzunoglu, Faik G.</creatorcontrib><creatorcontrib>Izbicki, Jakob R.</creatorcontrib><creatorcontrib>Pantel, Klaus</creatorcontrib><creatorcontrib>Bockhorn, Maximilian</creatorcontrib><creatorcontrib>Reeh, Matthias</creatorcontrib><title>Prospective Comparison of the Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of a Single Patient's Cohort With Esophageal Cancer</title><title>Annals of surgery</title><addtitle>Ann Surg</addtitle><description>OBJECTIVE:Aim of this prospective study was to evaluate the prognostic significance of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) in 1 cohort of patients with esophageal cancer (EC). BACKGROUND:Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patientʼs cohort has not been described before. METHODS:In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3. RESULTS:Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P &lt; 0.001, respectively). CONCLUSIONS:This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.</description><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - surgery</subject><subject>Aged</subject><subject>Bone Marrow - pathology</subject><subject>Carcinoma, Squamous Cell - mortality</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - surgery</subject><subject>Esophageal Neoplasms - mortality</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophageal Neoplasms - surgery</subject><subject>Esophagectomy</subject><subject>Female</subject><subject>Humans</subject><subject>Ilium - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Neoplastic Cells, Circulating</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Survival Rate</subject><issn>0003-4932</issn><issn>1528-1140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUV2P1CAUJUbjjqv_wBje9KUrFNrC41rXj2SMxl3jY8PQ2ylKoQLdiX_M3yd1VmM0URJC4J5z7uUchB5SckaJbJ5ebs_PyG-LcVLfQhtalaKglJPbaLO-Flyy8gTdi_ETIZQL0txFJ4xSIahsNujbu-DjDDqZa8Ctn2YVTPQO-wGnEXCu7p2PyWj8HixcK6dhrbUm6MWqZNweXy2TD7gFayM2Dj-z3vdYuR4_NzHCZJxK0P-F8g7wGxWCP6x6Cl9mKZsbZk1w6XHMw4w-JPzRpBFfRD-Pag_K4nYdIdxHdwZlIzy4OU_RhxcXV-2rYvv25ev2fFtoTmhdAJc1ZQwoo6whYmg0HWTdc0F3u1r2ipPdDlitB1JxCbyR2TGpdSPLSosKBDtFT466c_BfFoipm0zU-RPKgV9iV2bXCa8quUL5EaqzozHA0M3BTCp87Sjp1sS6nFj3Z2KZ9uimw7KboP9F-hlRBogj4OBtghA_2-UAoRuzGWn8nzb_B_UHrq5EUZKSkjJfirxpzb4DMdqzIg</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Konczalla, Leonie</creator><creator>Ghadban, Tarik</creator><creator>Effenberger, Katharina E.</creator><creator>Wöstemeier, Anna</creator><creator>Riethdorf, Sabine</creator><creator>Uzunoglu, Faik G.</creator><creator>Izbicki, Jakob R.</creator><creator>Pantel, Klaus</creator><creator>Bockhorn, Maximilian</creator><creator>Reeh, Matthias</creator><general>Lippincott Williams &amp; Wilkins</general><general>Copyright Wolters Kluwer Health, Inc. 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BACKGROUND:Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patientʼs cohort has not been described before. METHODS:In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3. RESULTS:Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P &lt; 0.001, respectively). CONCLUSIONS:This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.</abstract><cop>United States</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>31188197</pmid><doi>10.1097/SLA.0000000000003406</doi><tpages>7</tpages></addata></record>
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source MEDLINE; Journals@Ovid Complete; PubMed Central
subjects Adenocarcinoma - mortality
Adenocarcinoma - pathology
Adenocarcinoma - surgery
Aged
Bone Marrow - pathology
Carcinoma, Squamous Cell - mortality
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - surgery
Esophageal Neoplasms - mortality
Esophageal Neoplasms - pathology
Esophageal Neoplasms - surgery
Esophagectomy
Female
Humans
Ilium - pathology
Male
Middle Aged
Neoplasm Staging
Neoplastic Cells, Circulating
Prognosis
Prospective Studies
Survival Rate
title Prospective Comparison of the Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of a Single Patient's Cohort With Esophageal Cancer
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