Endocrine Abstracts

Background: Matrix metalloproteinase-9 (MMP-9) is overexpressed in almost all human cancers (including thyroid). High serum levels are generally associated with an adverse prognosis, although the evidence related to thyroid cancer is still controversial.

Aim: We aimed to evaluate pre- and post-surgical serum MMP-9 levels for its diagnostic and prognostic value in a series of patients with benign thyroid disease (BD) or differentiated thyroid carcinoma (DTC).

Patients and methods: We evaluated 306 patients referred for thyroidectomy, aged 49.55±13.76 years, divided in 2 groups according to pathology: BD (N=173) and DTC (N=133). Sera were collected before surgery in all patients and 1-2 months after surgery in a subset of 66 patients (41 BD, 25 DTC). All sera were stored at -80⁰C until MMP-9 was measured, after a median storage of 24 (range 7-45) months. MMP-9 was measured by Elisa (R&D Systems).

Results: Low MMP-9 values were detected in older samples of both BD and DTC patients, and a significant correlation was found between MMP-9 levels and storage duration (r=−0.449, P<0.001), suggesting that continuous MMP-9 degradation occurs in frozen samples. Median pre-op MMP-9 did not differ significantly between BD and DTC patients (630 ng/ml vs 581 ng/ml), even after correcting for storage duration in multiple regression analysis. After stratifying by storage duration, no MMP-9 difference was noted in cancer patients, irrespective of multifocality, invasiveness, pathological stage or histological subtype. After surgery, median MMP-9 decreased significantly in both BD (from 977 to 833 ng/ml, P=0.02) and DTC patients (from 931 to 718 ng/ml, P=0.02), suggesting that both benign and neoplastic nodules contribute to serum secretion. Post-op serum MMP-9 was significantly lower in DTC vs BD patients (P=0.019), possibly reflecting a more complete thyroidectomy in oncologic patients. In 5 DTC patients (20%) MMP-9 levels increased post-surgery by >20%, and 2 of them had high stimulated thyroglobulin on follow-up, so a more careful follow-up might be warranted for these patients; however 11 BD patients (26.8%) also presented with unexplained higher post-op MMP-9 levels.

Conclusion: Serum MMP-9 cannot distinguish benign from malignant thyroid disease. The MMP-9 dynamic after surgery remains incompletely explained, but postop MMP-9 may be useful in selecting cancer patients who require additional therapy. Because of sample instability during storage, careful protocols need to be established for standardisation of MMP-9 measurement. Since most published studies are conducted on bio-bank samples, comparison between studies must be conducted with care.