Expression of cytokeratin-19 (CK19) in the classical subtype of papillary thyroid carcinoma: the experience of one center in the Silesian region

Introduction. Cytokeratin-19 (CK19) is recognized as a reliable tumor marker of papillary thyroid carcinoma (PTC). The general prognosis in the classical subtype of PTC (CSTPTC) remains favorable, but some cases can be very aggressive. The aim of this study was to evaluate the localization and intensity of immunohistochemical CK19 expression in CSTPTC and its associations with the clinical and pathological characteristics of patients with CSTPTC in the Silesian region. Material and methods. All the available clinical and histopathological data for 149 patients with CSTPTC from the Silesian region were retrospectively analyzed. The group consisted of 135 (90.6%) women and 14 (9.4%) men (mean age and SD: 52.3 ± 15.0). All these patients with CSTPTC underwent surgery at the same center between 2008 and 2013; the follow-up period was 24 to 90 months (mean and SD: 47 ± 20). Results. In 142 (95.3%) of the patients with CSTPTC, positive cytoplasmic staining of CK19 was found. A higher expression of CK19 was observed in the group of patients without the recurrence of the disease (p = 0.015). CK19 expression was not associated with age, gender, tumor focality, disease stage, tumor size (pT), lymph node involvement (pN), or distant metastases (pM). Conclusions. Decreased CK19 expression in CSTPTC cases with relapse suggests that it plays a role in the carcinoma progression of CSTPTC. The association between lower CK19 expression and patients’ unfavorable postoperative course could suggest its possible role as a marker of CSTPTC poor prognosis

ACE and ACE2 expression in normal and malignant skin lesions

 The renin-angiotensin system (RAS) is known mainly as a regulator of cardiovascular homeostasis. However, it has also been shown to mediate processes such as proliferation, apoptosis, angiogenesis, and carcinogenesis. Nonmelanoma skin cancers (NMSC) — including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — are among the most common cancers. The aim of the present study was to determine the immunohistochemical expression of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), and Ki-67 antigen in archival samples of normal skin, actinic keratosis, and malignant skin lesions. Cytoplasmic-nuclear ACE immunoreactivity was observed in 99% of examined cases of both normal skin and cancers. Significantly higher ACE immunoreactivity occurred in normal skin, as compared with BCC and SCC (p < 0.01, p < 0.0001, respectively). Additionally, ACE immunoreactivity was also significantly higher in BCC, compared with SCC (p < 0.05). ACE2 immunoreactivity was noted in basal epidermal layers and in sebaceous gland cells in normal skin, though not in NMSC. These novel observations suggest that ACE and skin RAS may be involved in the pathogenesis of malignant skin lesions.

Effects of massage on the expression of proangiogenic markers in rat skin

  Introduction. Massage is a physiotherapeutic treatment, commonly used in both therapy and restoration of normal body functions. The aim of this work was to determine the effects of skin massage on stimulating the expression of angiogenesis-initiating factors, i.e. VEGF-A, FGF-2 (bFGF) and CD34 and on skin regeneration processes. Material and methods. The study was conducted on 48 Buffalo strain rats, randomly divided into two groups. In the first group (M, the massaged group), massage was applied five times a week for 7 weeks. In the second study group (C, the control group), the massage was omitted. Massage consisted of spiral movements at the plantar surface of skin for 5 min on each rear extremity. The gene expression of proangiogenic factors, including VEGF-A, FGF-2, CD34 at the mRNA level was determined using real-time PCR. Immunohistochemistry was performed on paraffin sections of rat skin to determine VEGF-A, FGF-2 CD34 and Ki-67expression. Results. An increase in mRNA expression in the skin of the rat’s rear extremity for VEGF-A and FGF-2 in the first week of the experiment was shown in the M group compared with the control rats. The upregulation of CD34 mRNA expression was also observed in the M group. We observed positive correlations between VEGF-A mRNA expression and the expression of mRNA for FGF-2 and CD34, as well as correlation between the expression of mRNA for FGF-2 and CD34. The immunohistochemical expression of VEGF-A, FGF-2 and CD34 was at a much lower level in the skin of control rats relative to the skin of massaged animals. Moreover, significantly higher immunoreactivity was shown for nuclear protein Ki-67 in epidermal cells in the M group compared with the C group. Conclusions. Rat skin massage increased the expression of the main angiogenesis-stimulating factors and the proliferative activity of epidermal cells, which can stimulate skin regeneration and tissue repairing processes

Increased skeletal muscle expression of VEGF induced by massage and exercise

Introduction. Numerous investigations have been carried out to describe the role of massage in preparing for and restoring efficiency after physical exercise. Furthermore, vascular endothelial growth factor (VEGF) enhances blood vessel growth, and in effect contributes to the regeneration of tissues. Since its expression in active skeletal muscles has not been yet determined, the aim of this study was to investigate whether muscle massage performed before and during running exercise affects the expression of VEGF-A in muscles. Material and methods. The study was carried out on 75 adult Buffalo rats subjected to running exercise training for 10 weeks. Rats were massaged prior (group PM) or during exercise (group M) or were not massaged (group C). The massage consisted of spiral movements along the plantar surface of flexor digitorum brevis muscle. After 1, 3, 5, 7 and 10 week of training, five rats from every group were anesthetized and immunohistochemistry, Western blot, and PCR analyses were performed on obtained muscle tissue to determine VEGF-A expression. Results. After the first week of training, a significant increase of VEGF-A gene expression analyzed by qPCR in muscle tissue was observed in the PM group, whereas in the third week, the predominant growth of studied marker was seen in the M group. Increased VEGF-A expression on the protein level was observed in both massaged groups following the first week. A moderate positive correlation was found between the expression of the VEGF-A gene and protein in all experimental groups (r = 0.389). Conclusion. Short-term repeated massage may contribute to processes of creation of new and development of already existing vascular networks in the skeletal muscle tissue during increased exercise

Expression of Zyxin in Non-Small Cell Lung Cancer—A Preliminary Study

Background: The potential involvement of zyxin (ZYX) in carcinogenesis has been investigated in many cancer types. However, there are a limited number of studies on the role of ZYX in the progression of non-small cell lung cancer (NSCLC). Since lung cancer is one of the most frequently diagnosed carcinomas, the aim of our study was to determine the localization and expression levels of ZYX in NSCLC and to correlate the results with the clinicopathological data. Materials and Methods: The expression of ZYX was assessed in NSCLC cases and in cell lines representing this tumor type. Levels of ZYX were determined in the clinical material using immunohistochemistry (IHC) and Western Blot. Real-time PCR was used to assess ZYX mRNA levels. The expression of ZYX was also checked in NSCLC cell lines using real-time PCR, Western Blot, and immunofluorescence/immunocytochemistry. Results: The results showed lower levels of ZYX in NSCLC cells compared with control tissues. This trend was observed at the protein and mRNA levels. The assays on the NSCLC model also demonstrated lower levels of ZYX in cancer cells compared with control cells. Conclusions: The decreased expression of ZYX in NSCLC may indicate a suppressor role of this protein in NSCLC

Role of PD-L1 Expression in Non-Small Cell Lung Cancer and Their Prognostic Significance according to Clinicopathological Factors and Diagnostic Markers

Background: The latest immunotherapy, used in the treatment of non-small cell lung cancer (NSCLC), uses monoclonal antibodies directed against programmed death ligand 1 (PD-L1) to inhibit its interaction with the PD-1 receptor. Elevated levels of PD-L1 expression were observed on NSCLC cells. The association between PD-L1 expression and clinicopathological features is still unclear. Therefore, we examined this relationship and also compare PD-L1 expression levels with Ki-67, p63 and TTF-1. Methods: 866 samples of NSCLCs were used to prepare tissue microarrays (TMAs) on which immunohistochemical (IHC) reactions were performed. Changes in the level of CD274 (PD-L1) gene expression in 62 NSCLC tumors were tested in relation to 14 normal lung tissues by real-time PCR reactions (RT-PCR). Results: PD-L1 expression was observed in 32.6% of NSCLCs. PD-L1 expression was increased in higher malignancy grades (G) (p < 0.0001) and in higher lymph node status (pN) (p = 0.0428). The patients with low PD-L1 expression had longer overall survival compared to the group with high expression (p = 0.0332) in adenocarcinoma (AC) only. Conclusions: PD-L1 expression seems to be associated with increased tumor proliferation and aggressiveness as well as shorter patient survival in NSCLC, predominantly in the AC group

The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell–cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p p p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics