Endocrine Abstracts

It is believed that differentiated thyroid tumors (DTC) metastasize via different pathways: papillary carcinoma (PTC) usually via lymphatic spread whereas follicular cancers (FTC) mainly hematogenously. However, the mechanism/s contributing to these tumors invasion is not fully understood.

We examined the expression of lymphatic endothelial markers: Podoplanin (type-1 transmembrane mucin-like glycoprotein) and Prox1 (Prospero homeobox protein 1) in the PTC and FTC derived cell lines and series of DTC using quantitative Real-Time PCR (Q-RT-PCR), Western blot and immunochemical (IHC, IF) methods.

Podoplanin (PDPN) was highly expressed on both transcript and protein levels in papillary cell lines BcPAP and TPC1 whereas follicular cell lines: FTC-133, CGTH-W-1 and ML-1 were negative. Papillary tumor cells showed PDPN mostly restricted to and distributed in the cytoplasm. Cell lines with podoplanin expression showed low or undetectable Prox1 transcript level. By contrast PDPN negative FTC cell lines highly expressed Prox1 mRNA. There was no correlation between Prox1 protein and transcript. In all examined cell lines Prox1 protein was present at similar level exhibiting diffuse nucleocytoplasmic pattern.

The majority (72/120) of PTC and all FTC tissues were PDPN negative. However, in 48/120 (40%) of PTC cases podoplanin was expressed in cytoplasm of tumor cells with heterogonous intensity. This cytoplasmic neoexpression was correlated with patients age. Normal thyroid (NT) and peritumoral tissue (PT) cells were totally negative. In these tissues antibody labeled solely lymphatic vessels used as internal positive control. Prox1 protein was strongly expressed in the cytoplasm, weakly in some nuclei of PDPN positive PTC and clearly in the nuclei of NT.

Our study is the first to demonstrate the difference in the expression of lymphatic specific markers podoplanin and nuclear transcription factor Prox1 in DTCs. This might suggest different spreading pathways of PTC and FTC. Further on-going studies will define this mechanism/s and its potential implications.

This work was supported by CMKP 501–1–25–01–11.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.