Endocrine Abstracts

Aim

To assess the relative expression of tissue inhibitor of metalloproteinase-1 gene (TIMP1) and chitinase-3-like protein 1 gene (CHI3L1) in fine-needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP-1 and chitinase-3-like protein 1 also known as YKL-40) in patients with histologically confirmed papillary thyroid cancer (PTC) and with benign nodules. Further, we evaluated the correlation between the gene expression and the circulating protein product.

Materials and methods

Eighty subjects (72 females, 8 males, mean age of 40.6 ± 11.3 years) were recruited from the routine patient flow referred for FNAB of thyroid nodules in one tertiary center. Forty patients with cytology Bethesda V and VI were operated and PTC was confirmed. The other 40 patients were with benign cytology (Bethesda II) and were considered a benign group. TIMP-1 and YKL-40 serum levels were measured in all subjects. The gene expression of TIMP1 and CHI3L1 was assessed in cytological specimens from 20 patients with PTC and 20 benign cases using quantitative real-time PCR.

Results

The PTC group was sex-matched with the benign group and the male-to-female ratio was 1:9. There was no significant difference between the mean age in the study groups (P = 0.922). The relative expression of TIMP1 and CHI3L1, assessed in FNAB washouts, was significantly higher in the PTC group than in the benign nodule group (P <0.001 for TIMP1; P = 0.018 for CHI3L1). The serum level of TIMP-1 was significantly higher in the PTC group compared to the benign group (82.0 ng/ml; 48.2–133.6 ng/ml vs. 91.8 ng/ml; 38.1–164.5, P = 0.036). We did not find significant difference in YKL-40 levels between the two study groups (71.4 ng/ml; 42.0–206.4 ng/ml in the benign group vs. 71.0 ng/ml; 20.4–229.2 ng/ml in the PTC group, P = 0.447). There was no correlation between TIMP1 and CHI3L1 expression and the serum levels of their protein products TIMP-1 and YKL-40 (P = 0.089, P = 0.517, respectively). TIMP1 relative expression showed better diagnostic value compared to CHI3L1 gene (P = 0.037) and to serum TIMP-1 (P = 0.004).

Conclusions

The increased expression of TIMP1 and CHI3L1 implies a possible role of these genes in the PTC carcinogenesis. Their identification in FNAB washouts could be used as additional diagnostic marker.