[Role of tenascin С in triple-negative breast cancer]

to establish a relationship between the main markers tumor stem cells (TSCs), CD44, and CD24, the level of tenascin C production, and chemoresistance in triple-negative breast cancer (BC).

Thirty biopsy specimens from triple-negative BC patients who had conventionally received preoperative chemotherapy followed by surgery were selected in the investigation. All the selected patients were conventionally assigned to neoadjuvant polychemotherapy (PCT) with paclitaxel and carboplatin. The surgical specimens were analyzed in relation to the degree of a tumor morphological response to PCT. The magnitude of the health-promoting effect of neoadjuvant therapy was evaluated according to the residual cancer burden (RCB) system using an on-line calculator; RCB was categorized into classes (from RCB-0 to RCB-III). The markers CD44, СD24, and tenascin C were identified by the standard immunoperoxidase method in the primary biopsies.

Varying morphological responses of triple-negative breast cancer to PCT were revealed, which showed resistance in 60% of the cases. The chemoresistance found in most (87%) cases coincided with the identification of the CD44+/CD24low/- profile. The detection of the higher production of the extracellular matrix tenascin C participating in the formation of the TSC niche fully combined with the CD44+/CD24low/- phenotype; while the maximum response to tenascin C was noted in the cases differing in not only a lack of responses to PCTs, but also in the most aggressive course in conjunction with metastatic disease.

Immunohistochemical analysis shows that the unique association between the CD44+/CD24low/- phenotype and the pronounced production of tenascin C may have a prognostic potential, prospectively indicating the inefficiency of neoadjuvant PCT, in particular that with platinum derivatives, which is used for the standard treatment of triple-negative BC. Taking into account the role of tenascin C in invasion, metastasis, and chemoresistance, it per se may be considered as a promising target for the targeted and/or combined therapy of triple-negative BC.