Endocrine Abstracts

Introduction: Tubulin is a multifunctional cytoskeletal protein involved in key cellular processes, including cell movement, intracellular transport and mitosis. An increased expression of βIII-tubulin (TUBB3) has been observed in several cancer types and associated with aggressive and drug refractory disease.

Expression of claudins (CLDNs), the main component of tight junctions, is frequently altered in human cancers, including papillary thyroid carcinoma (PTC). E-cadherin (E-CD) plays a critical role in the maintenance of epithelial phenotype. Loss of E-CD expression is considered as the hallmark of epithelial-to-mesenchymal-transition.

Aim: To analyze the presence of TUBB3 protein in PTC samples in relation to expression of molecules with cell-cell adhesive role (E-CD, CLDN1 and CLDN7).

Methods: The study included 70 PTCs, 17 lymph node metastases, seven follicular adenomas and five nodular hyperplasias.

Results: No positivity was observed in follicular epithelium, nodular goiter and follicular adenoma. In PTC samples, the reactivity was heterogeneous and demonstrated strong cytoplasmic staining in widely infiltrating PTCs associated with fibrous stroma, particularly at invasive front of tumour, or in moderately differentiated PTCs with loss of cellular polarity/cohesiveness. In these areas, CLDN1/7 expression were decreased or less intense in comparison with the center of neoplasia. Decreased E-CD staining was also observed at invasive front of tumour. Conversely, PTCs with expanding margins or well-developed follicles were constantly negative.

The majority of lymph node metastases showed strong TUBB3 immunoreactivity.

Conclusions: We report for the first time TUBB3 expression in thyroid tissue.

In analogy with carcinomas of other sites, TUBB3 expression appears to be increased in PTCs with ‘aggressive’ histological features, thus suggesting that changes in tubulin isotype composition could modulate the invasive and metastatic potential of cancer cells.

The decreased CLDNs and E-CD expression in combination with the TUBB3 positivity, at invasive front of tumour, could be a possible morphological indicator of epithelial-to-mesenchymal-transition in PTC.

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 research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.