BackgroundThe aim of the study was to investigate if parameters associated with human epidermal growth factor receptor type 2 (HER2) status (HER2 gene copy number, HER2/CEP17 ratio or polysomy of chromosome 17) are related to various biological features potentially responsible for trastuzumab resistance (PTEN, IGF-1R, MUC4, EGFR, HER3, HER4, and mutation status of PIK3CA) as well as their influence on survival of HER2-positive breast cancer patients treated with adjuvant chemotherapy and trastuzumab.Patients and methodsThe investigated group consisted of 117 patients with invasive ductal breast cancer (T≥1, N≥0, M0) with overexpression of HER2, who underwent radical surgery between 2007 and 2014. Status of ER, PR, and HER2 expression was retrieved from patients’ files. HER2 gene copy number was investigated by fluorescence in situ hybridization using PathVysion HER-2 DNA Probe Kit II. Expression of PTEN, IGF-1R, MUC4, EGFR, HER3, and HER4 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. PIK3C mutation status was determined by qPCR analysis.ResultsOverexpression of HER2 protein (IHC 3+) and ER negativity corresponded to higher HER22 copy number and HER2/CEP17 ratio (.<0.001). Tumors with polysomy were characterized by higher HER22 gene copy number but lower HER2/CEP17p ratio (p<0.026, p<0.001). Patients with tumors featuring HER3 immunonegativity or low HER2/CEP17 ratio (#4) were characterized by 100% metastasis-free survival (.=0.018, p=0.062).ConclusionPresence of both unfavorable factors, ie, HER3 expression and high HER2/CEP17 ratio, allowed to distinguish a group of patients with worse prognosis (.=0.001).
Introduction. It has been suggested that the metastatic potential of neoplastic cells can be predicted on the basis of their biological features, including expression of proteins involved in the epithelial to mesenchymal transition (EMT). Therefore, the purpose of this work was to (1) evaluate the expression of EMT markers: ZEB2, vimentin, N-cadherin, TWIST, PTEN, survivin, E-cadherin, Ki-67 and GLUT-1, (2) assess mutation status of two genes: PIK3CA and KRAS, and (3) investigate the potential relationships between the studied biomarkers and clinicopathological factors in clear-cell renal cell carcinoma (ccRCC). Material and methods. Tumor tissue samples (embedded in paraffin blocks) from 159 patients undergoing radical nephrectomy were analyzed. Proteins expression was evaluated immunohistochemically. DNA mutations were analyzed on DNA isolated from tumor tissue and amplified by real-time PCR detection using suitable fluorescent labeled TaqMan assays. Results. One hundred and seven men and 52 women of mean age of 63.1years were enrolled. Fifty four cancers at pTNM stage I-II and 98 at pTNM III-IV stage were diagnosed. There were 30 Fuhrman grade G1, 61 Fuhrman G2, 49 Fuhrman G3 and 19 Fuhrman G4 tumors. A negative correlation between ZEB2 (p = 0.047, r = -0.172) or E-cadherin expression (p = 0.027, r = -0.191) and TNM was observed. Positive association between grade and Ki-67 (p < 0.001), survivin (p < 0.001), vimentin (p < 0.001) immunoreactivity and negative association between TWIST expression (p = 0.029) or PTEN expression (p = 0.013) were found. Ki-67 expression was positively correlated with survivin (p < 0.001, r = 0.617), vimentin (p = 0.001, r = 0.251) and N-cadherin (p = 0,009, r = 0.207) immunoreactivity which can suggest tumor aggressiveness. TWIST was negatively correlated with E-cadherin (p < 0.001, r = -0.284), vimentin (p < 0.001, r = -0.297) and N-cadherin (p < 0.002, r = -0.241). ZEB2 was not associated with ccRCC grade but was negatively correlated with E-cadherin (p = 0.055, r= -0.153) and PTEN (p = 0.006). GLUT-1 expression was inversely linked to E-cadherin expression (p = 0.022, r= -0.182). Mutations in PIK3CA and KRAS genes were not found in any of the studied ccRCC tumors. Conclusions. Low-grade tumors showed higher expression of ZEB2 and TWIST proteins than high-grade tumors, which can suggest that EMT in ccRCC begins at early stages of tumor development and, therefore, evaluation of these proteins, together with other biomarkers, may be useful for assessment of the tumor metastatic potential.
Early recognition of prostate cancer (PC) based on biological markers could be helpful in identification of differences in benign and malignant lesions and facilitate further precise indication for more aggressive treatment. Therefore, the aim of our study was to assess expression of hTERT (human telomerase reverse transcriptase, a catalytic subunit of telomerase) and prostate-specific membrane antigen (PSMA), both considered to be markers of tumor aggressiveness. 140 low advanced PC specimens from patients who underwent radical prostatectomy were studied. Protein expression was assessed immunohistochemically on tumor sections and expressed as labeling index (LI), i.e. the percentage of positively stained cells. In case of telomerase, only nuclear staining and in case of PSMA, membrane and cytoplasmic staining, were considered as positive. The mean age of the patients was 62.9 ± 6.2 years. There were 75 (53.6%) well differentiated tumors (Gleason score 6), 52 (37.1%) moderately differentiated tumors (Gleason score of 7) and 13 (9.3%) poorly differentiated tumors (Gleason score 8-10). The mean pre-operative serum PSA was 9.9 ± SE 5.5 ng/mL, and the mean LI were 18.0 ± 1.5% and 44.1 ± 1.9%, for hTERT and PSMA, respectively. With increase of pathological tumor stage and tumor grade statistically significant increase of PSA serum concentration (P < 0.011) and PSMA (P < 0.004) expression was noticed, however, for expression of telomerase the relation was opposite one. The observed in higher pTNM stages and tumor grades decrease in nuclear expression of hTERT was caused by translocation of the subunit to the cytoplasm, what may indicate extranuclear telomerase activity independent of telomere lengthening, hence, it cannot be considered as a marker of malignancy. Higher PSMA expression in higher pTNM stages and tumor grades suggest that PSMA may be a good marker of biological aggressiveness suitable for patients' selection for more aggressive treatment.
Our results suggest that in some cases expression of markers in lymph node metastases might bring additional prognostic information to that obtained from primary tumor.
Biological potential of plant extracts are widely described. Because their oral or topical administration is usually recommended, intestinal mucous and skin are the first surfaces exposed to such preparations. Therefore, we asked the question whether phenolic and non-polar fractions of the extracts from fruits, twigs, and leaves of sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) would be able to modulate the functions of human physiological barrier. The study was carried on caucasian colon epithelial-like Caco-2 cells and human foreskin fibroblasts HFF-1 line. Cell secretory activity (ELISA), the expression of cell surface molecules (flow cytometry), cell migration during wound healing in vitro (scratch assay) were assessed. It was demonstrated for the first time, that sea buckthorn extracts can improve intestinal and skin barrier by increasing of ICAM-1 expression on colon epithelial cells and intensification of IL-8 production by fibroblasts. On the other hand, an inhibition of fibroblasts migration in the presence of those preparations was noted. Therefore, greater attention should be paid on precise description of plant extracts effect depended on target cells and their role to give adequate recommendations for such preparations use.
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