Cystathione β-Synthase Is Increased in Thyroid Malignancies

Abstract

Background: Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (H₂S) and cystathione, via the trans-sulfuration pathway. CBS protein expression levels are increased in several different human malignancies, with increased protein expression correlating with parameters such as tumor stage, anaplasia, metastases, and chemotherapy resistance.

Materials and methods: This study employed tissue microarrays to examine CBS expression in benign thyroid tissue, thyroid oncocytomas, thyroid follicular adenomas, and in follicular, papillary, anaplastic, and medullary thyroid carcinomas.

Results: CBS expression was increased in all thyroid carcinomas types compared to benign thyroid tissue, but not in thyroid follicular adenomas or oncocytomas. A similar pattern was observed for nicotinamide phosphoribosyltransferase (NAMPT) tissue microarray analysis comparing thyroid adenomas and follicular carcinomas.

Conclusion: For the first time, we showed that an H₂S-syntheszing enzyme plays a role in thyroid malignancies. Additionally, our data suggest that CBS and NAMPT immunohistochemistry may be useful in differentiating follicular adenomas from follicular carcinomas.

Keywords: Cystathione β-synthase; NAMPT; follicular adenoma; follicular carcinoma; thyroid.

Figure 1.

Representative nicotinamide phosphoribosyltransferase immunostaining of benign thyroid (A), thyroid follicular adenoma (B), thyroid papillary carcinoma (C), thyroid follicular carcinoma (D) and thyroid anaplastic thyroid carcinoma (E). Original magnification ×400.

Figure 2.

Representative cystathione β-synthase immunostaining of benign thyroid (A), thyroid follicular adenoma (B), thyroid papillary carcinoma (C), thyroid follicular carcinoma (D), thyroid medullary carcinoma (E), thyroid oncocytoma (F), and thyroid anaplastic carcinoma (G). Original magnification ×400.