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The Chemokine Receptors CXCR4 and CCR7 are Associated with Tumor Size and Pathologic Indicators of Tumor Aggressiveness in Papillary Thyroid Carcinoma

¹ Department of Surgery, New York-Presbyterian Hospital/Weill Cornell Medical Center, 525 E. 68th St., K-707, New York NY 10065, USA
² Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA

Correspondence: Address correspondence and reprint requests to: Patrick L. Wagner, MD; E-mail: plw9001{at}nyp.org

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. [Statistics: 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).

Conclusion: 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.

Key Words: Papillary thyroid carcinoma • CXCR4 • CXCL12 • CCR7 • CCL21 • Chemokine receptors