"The potential role of CXCR4 and SDF-1 as indicators of tumor aggressiviness in patients with conventional papillary thyroid carcinoma"

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 SDF-1 and its chemokine receptors, CXCR4, in a series of PTCs, considered as low risk for tumor size and hystotypes. In this study, we correlated CXCR4 and SDF-1 with indicators of clinical and tumor aggressiveness, including age, gender, tumor size, extrathyroidal extension, multifocality and lymph node metastasis. Methods: CXCR4 as well as its specific chemokine ligand, SDF-1 , were assessed in 48 PTCs using a semiquantitative measure of immunohistochemical (IHC) staining intensity for each molecule. Staining intensity was compared with clinicopathological features. Expression in CXCR4 and SDF-1 mRNA levels were sought in a subset of tumors, using gene microarrays and quantitative RTPCR. Results: In 29 cases, the PTC was associated with chronic thyroiditis. High-intensity IHC staining for CXCR4 correleted with T1 (p=0.003), classical variant (p=0.02) and lymph node metastasis at initial diagnosis (p=0.01). In contrast SDF 1 correlated with female gender (p =0.05), but this association was not shown following multivariate analyses. Conclusion: In our study, the expression of CXCR4 and its ligand are more frequent in tumors that have a smaller dimension and a classical variant of PTC. Therefore, CXCR4 and its ligand are associated with lymph node metastasis involvement at the initial diagnosis, which is an indicator of negative prognosis. Finally, the chemokine pathways may be expressed early in PTC tumorigenesis. Although these markers are found in a less aggressive PTC variant, they may be responsible for early and preferential lymphnode neck metastases. Further studies are necessary to define the mechanisms underlying this association and to determine its potential prognostic and therapeutic implications.