S616-p-DRP1 associates with locally invasive behavior of follicular cell-derived thyroid carcinoma
- PDF / 1,441,359 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 4 Downloads / 162 Views
ORIGINAL ARTICLE
S616-p-DRP1 associates with locally invasive behavior of follicular cell-derived thyroid carcinoma Ana Rita Lima 1,2,3 Marcelo Correia1,2 Liliana Santos4,5 Catarina Tavares1,2 Elisabete Rios1,2,3,6,7 Sule Canberk1,2,3,8 Paula Soares1,2,3,6 Manuel Sobrinho-Simões1,2,6,7 Miguel Melo1,2,9,10 Valdemar Máximo1,2,3,6 ●
●
●
●
●
●
●
●
●
1234567890();,:
1234567890();,:
Received: 5 August 2020 / Accepted: 2 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Dynamin-related protein 1 (DRP1), a mitochondrial fission protein, and its active form phosphorylated at Serine 616 (S616-p-DRP1) have been increasingly associated with tumorigenesis and invasion in various tumor models, including oncocytic thyroid cancer (TC). In this study, the expression of DRP1 and S616-p-DRP1 and its relationship with patients’ clinicopathological characteristics, tumor genetic profiles, and clinical outcomes were assessed in a large series of follicular cell-derived TC (FCDTC). Methods Retrospective biomarker study characterizing the clinicopathological and immunochemistry DRP1 and S616-pDRP1 expression of a series of 259 patients with FCDTC followed in two University Hospitals. Results DRP1 expression was positive in 65.3% (169/259) of the cases, while the expression of the S616-p-DRP1 was positive in only 17.3% (17/98). DRP1-positive expression was significantly associated with differentiated tumors (67.7 vs. 48.0%; P = 0.049), non-encapsulated tumors (73.8 vs. 57.4%; P = 0.011) and thyroid capsule invasion (73.4 vs. 57.5%; P = 0.013). S616-p-DRP1-positive expression was significantly associated with tumor infiltrative margins (88.9 vs. 11.1%; P = 0.033), thyroid capsule invasion (29.8 vs. 3.1%; P = 0.043), lymph node metastases (23.3 vs. 8.1%; P = 0.012), and higher mean cumulative radioiodine dosage (317.4 ± 265.0 mCi vs. 202.5 ± 217.7 mCi; P = 0.038). S616-p-DRP1 expression was negatively associated with oncocytic phenotype (0.0 vs. 26.2%; P = 0.028). Conclusions S616-p-DRP1 is a better candidate than DRP1 to identify tumors with locally invasive behavior. Prospective studies should be pursued to assess S616-p-DRP1 role as a molecular marker of malignancy in TC and in patients’ risk assessment. Keywords Dynamin-related protein 1 Mitochondrial dynamics Thyroid cancer, Hürthle cell Thyroid neoplasms, Oncocytic Invasion ●
●
●
●
Introduction These authors contributed equally: Ana Rita Lima, Marcelo Correia Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02546-4) contains supplementary material, which is available to authorized users. * Ana Rita Lima [email protected] 1
2
3
4
5
Thyroid cancer (TC) is the most common endocrine malignancy, with a worldwide 5-year prevalence among all 6
Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Rua Alfredo Allen 208, 42
Data Loading...
