[Is there a claudin-low phenotype of breast cancer?] / Sushchestvuet li «nizkoklaudinovyi¼ fenotip raka molochnoi zhelezy?

The novel molecular subtype of breast cancer (BC), named "claudin-low", was described in 2007. It was characterized by the consistently low expression of genes involved in the formation of epithelial tight junctions in combination with the high activation of genes associated with the epithelial-to-mesenchymal transition, as well as tumor stem cell markers. The similar claudin- low subtype was later identified at the transcriptional level in bladder cancer, gastric cancer, and serous ovarian cancer. However, only in relation to BC, attempts were made to create a surrogate panel for immunohistochemical identification of this subtype in a manner like the intrinsic molecular BC subtypes identified using three main markers, such as ER, PR, and HER-2. At the same time, the ambiguity in the expression of claudins among the subtypes of BC, which is defined by various authors at the immunohistochemical level, as well as the absence of both the confirmed set of immunohistochemical criteria and a unified approach to their assessment, complicate these efforts. The purpose of the review is to show that the immunohistochemical identification of claudin-low subtype of BC is a separate problem that has significant limitations, needs standardization and has not yet reached diagnostic value.

[Role of tenascin С in triple-negative breast cancer]. / Rol' tenastsina S pri troinom negativnom rake molochnoi zhelezy.

AIM: 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). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[A change in the expression of membrane-associated proteins and cytoplasmic actin isoforms in the progression of human colon tumors]. / Izmenenie ékspressii membranoassotsiirovannykh belkov i tsitoplazmaticheskikh izoform aktina pri progressirovanii opukholei tolstoi kishki cheloveka.

Tumor progression is a complex process that also involves the restructuring of the actin cytoskeleton and the weakening of intercellular adhesive contacts due to the tumor cells that pass through the epithelial-mesenchymal transition (EMT). AIM: Тo identify correlations between clinical features, risk of progression and/or recurrence of human colon adenocarcinomas (CAC), and EMT-related tumor markers. MATERIAL AND METHODS: Descending colon and sigmoid colon adenocarcinoma samples were examined immunohistochemically. Formalin-fixed paraffin-embedded tissue sections were incubated with antigen-specific antibodies, then secondary antibodies labeled with fluorochromes, and the fluorescence intensity of microscopy images was analyzed. RESULTS: The cells of a tumor compared to those of intact colon tissue showed a weak staining of E-cadherin in the cell-cell contact areas. The reduced membrane staining and nuclear localization of ß-catenin were detected in moderately (G2) and poorly (G3) differentiated tumors. There were substantially decreased ß-actin levels in almost all tumor samples and increased γ-actin ones, mainly in the samples belonging to stage IV disease. CONCLUSION: A correlation was found between stage, tumor differentiation grade, risk for relapse or progression of disease, and the impaired expression of different EMT markers: total or partial loss of E-cadherin expression, ß-catenin reorganization in cell-cell contacts, and a change in the ratio of cytoplasmic actin isoforms in the late stages of CAC development. We believe that these molecular markers may have a prognostic potential.