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Clinical Implication of Activin A, Inhibin A, and Their Receptors mRNA Expression in Thyroid Papillary and Follicular Carcinomas

Aim: To determine clinical implications of activin A (ActA), inhibin A (InhA), and their receptors ActRI and ActRIIB mRNA expression profile testing in papillary (PTC) and follicular (FTC) thyroid carcinoma. Methods: Tissue samples were divided in 6 groups: 27 PTC, 21 FTC, 11 Hürthle cell carcinomas (HC), 16 follicular adenomas (FA), 15 Hürthle cell adenomas (HA) and 26 euthyroid multinodular goiters (MNG). RNA was isolated from 10-μm paraffin tissue sections. Gene expression was studied using reverse transcription-polymerase chain reaction (RT-PCR). An internal control gene was HPRT1. ImageQuantTL program was used for relative quantification of RT-PCR bands. Data, expressed as medians (interquartile ranges), were processed using Kruskall-Wallis test with Schaich- Hamerle post-hoc analysis. Results: InhA, ActA and ActRI, but not ActRIIB mRNA, were expressed in the majority of tissue samples. InhA mRNA was over- expressed in HA relative to FA (P=0.00044), FTC (P=10-3) and PTC (P=2.9x10-5). HC were indistinguishable from HA, as well as FTC from FA. In contrast, InhA mRNA was consistently overexpressed in Hürthle cell neoplasms when compared to follicular variants [181 (142-205) vs. 89 (70-112), HA vs. FA, P=5.5x10-5 and 164 (115- 176) vs. 98 (81-107), % HPRT1 mRNA, HC vs. FTC, P=7.9x10-5]. Moreover, InhA mRNA was over- expressed in metastatic PTC (n=10) relative to non-metastatic forms [99 (92-117) vs. 84 (76-88), % HPRT1 mRNA, pN0 vs pN1+, P=0.007] ; no other differences were observed between PTC, FTC and MNG. Additionally, ActRI mRNA expression was down- regulated in FA, FTC and PTC relative to MNG (P=1.8x10-5, 6.8x10-4 and 3.3x10-4), whereas ActA mRNA was under-expressed in PTC relative to FA and, marginally, HC (P=2.3x10-3and 8.6x10-3). Neither pT stage, nor age were related to mRNA expression in cancerous tissue specimens. Conclusion: Activin system is involved in the maintenance of homeostasis in normal and transformed thyrocytes: InhA, ActA and the activin signaling pathway are differentially affected by cell transformation over a broad spectrum of neoplastic phenotypes and may play role in thyroid tumorigenesis. Here, we implicate InhA mRNA expression as a possible marker of PTC aggressiveness, metastatic potential and progression.

Activin A ; Inhibin A ; Thyroid Papillary and Follicular Carcinomas

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