[The expression and significance of trefoil factor 3 and SDF-1/CXCR4 biological axis in papillary thyroid carcinoma]

Abstract

Objective: To study the expression of trefoil factor 3 (TFF3)with stromal cell-derived factor (SDF-1) and its receptor (CXCR4) in papillary thyroid carcinoma(PTC), and investigate the function of TFF3, SDF-1/ CXCR4 and the relationship among them during the tumor genesis,development and outcome of PTC.

Method: Detecting the expression of TFF3 and SDF-1/CXCR4 by immunohistochemical method (SP) in 92 cases of PTC and para-carcinoma tissue. Semiquantitative analysis of the results of immunohistochemistry was conducted by image analysis software.

Result: (1) TFF3 protein was expressed in the cytoplasm of cancer cells,while TFF3 was negative or weakly positive in follicular cells of para-carcinoma tissue. The positive expression rate of TFF3 was 92.39%, of which the strong positive rate of clinical stage III-IV accounted for 71.79% (42/59) and that of clinical stage I-II was 33.33% (11/33) (P < 0.01). The positive rate of TFF3 was significantly higher in the cases with lymph node metastasis than those without lymph node metastasis (100.00% vs 86.27%, P < 0.05). The AOD value of TFF3 was higher in PTC than in para-carcinoma tissue, that in cases with lymph node metastasis was higher than those without lymph node metastasis, and that in stage III-IV was higher than those in I-II (P < 0.05 or P < 0.05). (2) There was high expression of SDF-1 in the cytoplasm of malignant tissues. The para-carcinoma tissue was weakly positive or negative to SDF 1 and metastatic lymph nodes was weakly positive to SDF 1. The positive rates and AOD values of SDF-1 protein were similar to those of TFF3 in PTC,that is to say the positive rate and AOD values were higher in PTC than in para-carcinoma tissue, those in cases with lymph node metastasis were higher than those without lymph node metastasis, those in stage III-IV were higher than those in I-II, and those in patients older than 45 years old was obviously higher than those in patients under 45 years old (P < 0.05 or P < 0.01); CXCR4 was also mainly expressed in cytoplasm with few expression in nuclei, while negative or weakly positive in para-carcinoma. The positive rate and AOD values of CXCR4 in PTC were similar to SDF-1, meaning that they were higher in PTC than in para-carcinoma tissue and associated with the clinical stage, lymph node metastasis and age (P < 0.05 or P < 0.01). (3) There was positive relationship between TFF3 and SDF-1 as well as between SDF-1 and CXCR4 in PTC (r = 0.971, P < 0.01).

Conclusion: The high expression of TFF3, SDF-1 and CXCR4 in PTC are correlated with carcinogenesis and progression, and may play a significant role in evaluating the malignancy degree and progression of PTC.