**5. Conclusions**

In conclusion, our data have demonstrated that increased cytoplasmic Gal-3 expression can (i) significantly distinguish indolent NIFTP from invasive EFVPTC; (ii) assist in the early detection of thyroid tumors with aggressiveness and potential metastatic spread which can be suspected by the increased cytoplasmic Gal-3 expression; (iii) support its clinical application as a useful ancillary test to H&E histopathological diagnostic assessment in distinguishing invasive EFVPTC from NIFTP when there is no significant interference from LT.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/ 10.3390/cancers13122988/s1, Figure S1: Photomicrographs of IHC scoring of Gal-3 expression in thyroid tissue sections. Figure S2: ROC curve analysis showed each cut-off value of IHC scores. Table S1: The cut-off values for immunopositivity of cytoplasmic Gal-3 expression were compared to Sensitivity and Specificity via ROC analysis.

**Author Contributions:** Conceptualization and design, G.F., O.P.; methodology and validation, G.F.; cohort classification, O.P.; investigation, G.F. and O.P.; analysis, G.F., O.P. and R.S.C.; resources, J.L.F. and I.J.W.; writing—draft preparation, G.F.; review and editing, G.F., O.P.; R.S.C., J.L.F. and I.J.W.; project administration, G.F.; funding acquisition, I.J.W. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by The Mount Sinai Hospital Foundation of Toronto Da Vinci Gala Fundraiser and a donation from The Joyce Wolfish Estate, Mount Sinai Hospital Department of Medicine Research Fund (P.G.W.), Alex and Simona Shnaider Chair in Thyroid Cancer (I.J.W.).

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Sinai Health System Research Ethics Board (REB #07-0212-E).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Acknowledgments:** This work was supported by Paul G. Walfish (P.G.W.), who passed away on 28 July 2018.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses or interpretation of data, and in the writing of the manuscript or in the decision to publish the results.
