title: The chemokine receptors CXCR4 and CCR7 are associated with tumor size and pathologic indicators of tumor aggressiveness in papillary thyroid carcinoma.
abstract: BACKGROUND
  Functional chemokine receptors are expressed in many malignant tumors, including papillary thyroid carcinoma (PTC). These receptors promote tumor growth and metastasis in response to endogenous chemokines. The purpose of this study was to examine the expression of two chemokine receptors-CXCR4 and CCR7-in a series of PTCs. We hypothesized that CXCR4 and CCR7 would correlate with indicators of tumor aggressiveness, including tumor size, extrathyroidal extension (ETE), angiolymphatic invasion (ALI), and lymph node metastasis.
  
  
  METHODS
  CXCR4 and CCR7, as well as their specific chemokine ligands (CXCL12 and CCL21, respectively), were assessed in 88 PTCs from 65 patients using a semiquantitative measure of immunohistochemical (IHC) staining intensity for each molecule. Staining intensity was compared with clinicopathologic features including patient age, gender, tumor size, multifocality, ETE, ALI, and lymph node metastasis. Differences in CXCR4 and CCR7 mRNA levels were sought in a subset of tumors using gene microarrays and quantitative RT-PCR. [
  
  
  METHODS
  t test, Mann-Whitney U test; P < .05].
  
  
  RESULTS
  High-intensity IHC staining for CXCR4 was associated with larger tumor size (P = .02), while PTCs exhibiting ETE, ALI, or lymph node metastasis showed higher-intensity IHC staining for CCR7 than those without (P = .01, .03, and .01, respectively). CCR7 mRNA levels were also higher in tumors with ALI (P = .04).
  
  
  CONCLUSIONS
  Expression of CXCR4 and CCR7 by PTCs is associated with indicators of tumor aggressiveness, including tumor size, ETE, ALI, and lymph node metastasis. Further studies are necessary to define the mechanisms underlying this association and to determine its potential prognostic and therapeutic implications.
authors.affiliation: Department of Surgery, New York-Presbyterian Hospital/Weill Cornell Medical Center, 525 E. 68th St., K-707, New York, NY 10065, USA. plw9001@nyp.org
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Wagner
authors.forename: Tracy-Ann
authors.initials: TA
authors.lastname: Moo
authors.forename: Nimmi
authors.initials: N
authors.lastname: Arora
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Rasa
authors.initials: R
authors.lastname: Zarnegar
authors.forename: Theresa
authors.initials: T
authors.lastname: Scognamiglio
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fahey
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000328:Adult; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: C515370:CCR7 protein, human; C527276:CXCR4 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D054400:Receptors, CCR7; D019718:Receptors, CXCR4