SAT524 Relaxin: A Novel Marker for Pro-Tumoral Thyroid Cancer Microenvironment?

Abstract

Abstract Disclosure: A. Kotwal: None. R.G. Bennett: None. B. Swanson: None. W. Goldner: None. A. Yuil-Valdes: None. N. Whiteman: None. O. Shats: None. Background: Differentiated thyroid cancer (DTC) generally has a favorable prognosis, however, 30% have recurrence and progression hence there is a critical need to identify additional prognostic and potentially therapeutic markers. Relaxin inhibits the inflammatory macrophage type (M1) but promotes the anti-inflammatory macrophage type (M2) which is favorable for tumor growth, hence deserves to be investigated in the DTC tumor microenvironment (TME). Hypothesis: Relaxin is expressed in DTC and is associated with pro-tumoral macrophage infiltration. Methodology: A tissue microarray (TMA) with cores per specimen was created from surgical thyroid tissue from 55 adults with DTC localized to the neck. Fluorescent immunohistochemistry (FIHC) using antibodies against nucleus (DAPI), macrophage (CD68), M2 macrophage (CD163), and relaxin (RLN2) was performed on this TMA. Gene (qPCR) and protein (Western blot) expression of RLN2 and its receptor RXFP1 in thyroid cell lines were also identified. Results: The median age was 50 years (range 19-78), 73% were females, 65% were classic and 24% follicular variant of papillary thyroid cancer. 87% were AJCC stage I while the rest were stage II; 54% were ATA low risk, 31% intermediate risk and 15% high risk. Relaxin was strongly expressed in human DTC tissue and had a strong positive correlation with the abundance of CD163 (M2 macrophages) with an r2=0.55 (p<0.0001) but did not colocalize with macrophages. In vitro experiments demonstrated variable expression of relaxin and its receptor RXFP1 in human thyroid cell lines. Conclusions: Our pilot study concluded that relaxin expression and its positive correlation with pro-tumoral M2 macrophage infiltration in the TME make it a potential biomarker for the occurrence and prognosis of DTC in humans. Thyroid cell lines’ expression of relaxin and its receptor RXPF1 complement the TMA findings, hence may serve as a model for developing therapeutic options against advanced thyroid cancer. Presentation Date: Saturday, June 17, 2023