Biomedical subjects

Andrzej K Bednarek

Publications and source records attributed to Andrzej K Bednarek.

6 recordsLinked to original sources

PubMed2006

A comparative assessment of HER2 status in operable breast cancer by real-time RT-PCR and by immunohistochemistry.

BACKGROUND: The most commonly used methods for detecting HER2 gene amplification in breast cancer are immunohistochemistry and fluorescence in-situ hybridization. The aim of this retrospective study was to assess HER2 expression by real-time RT-PCR. MATERIAL/METHODS: Expression of HER2 was analyzed by real-time RT-PCR and immunohistochemistry in specimens of invasive ductal breast cancer tissue obtained from 131 women during radical mastectomy. RESULTS: There was a highly significant difference in mean relative gene expression between HER2-positive and HER2-negative patients as assessed by immunostaining (22.10+/-41.89 vs. 3.17+/-8.76; p<0.001). With a median follow-up of 56 months, the cancer-specific survival of HER2-positive patients assessed by RT-PCR was worse in all cases and in the node-positive group. In multivariate analysis, HER2 status was an independent prognostic factor in all patients. CONCLUSIONS: Real-time RT-PCR is a valuable method for determining HER2 status, but the selection of the cut-off point of the relative gene expression differentiating between HER2-negative and -positive tumors is essential.

Adult↗

PubMed2006

Ki-67 expression in operable breast cancer: a comparative study of immunostaining and a real-time RT-PCR assay.

The main purpose of this retrospective study was to compare Ki-67 expression in operable breast cancer examined by immunostaining and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Relations between Ki-67 and classic prognostic factors were also investigated, and the prognostic relevance of Ki-67 expression was examined. Expression of Ki-67 was analyzed in specimens of invasive ductal breast cancer tissue obtained from 131 women during radical mastectomy. There was a significant, but weakly positive, correlation between Ki-67 expression assessed by immunostaining and real-time RT-PCR (tau=0.154, p=0.005). Higher Ki-67 expression in immunostaining and RT-PCR was more often seen in grade 3 tumors (p<0.001 and p=0.026, respectively). No significant relationship with age, disease stage, nodal involvement, estrogen receptor or HER2 status was found. In a univariate and multivariate analysis of cancer-specific survival with a median follow-up of 56 months, Ki-67 expression determined by immunostaining or real-time RT-PCR was no prognostic factor. We demonstrated that Ki-67 expression levels measured by immunostaining and real-time RT-PCR were weakly concordant, and both were related to higher tumor grade. Ki-67 expression did not influence survival.

Adenocarcinoma↗

PubMed2006

Cyclin E expression in operable breast cancer quantified using real-time RT-PCR: a comparative study with immunostaining.

OBJECTIVE: The main purpose of this retrospective study was to compare cyclin E expression levels in operable breast cancer patients determined using real-time RT-PCR and immunostaining. The prognostic relevance of cyclin E was also investigated. METHODS: Specimens of invasive ductal breast cancer tissues obtained from 124 women during radical mastectomy were analyzed. RESULTS: Of the tumor samples, 40.3 and 59.7% showed high expression of cyclin E in RT-PCR and immunostaining, respectively. The overall agreement probability was 0.032 according to Scott's pi statistic. With a median follow-up of 55.5 months, cyclin E expression assessed using immunostaining was an independent negative prognostic factor in the node positive group (hazard ratio 3.1; 95% CI 1.0-9.2; P = 0.045). Cyclin E expression correlated with absence of steroid receptors and younger age. RT-PCR results did not predict survival in any group of patients. CONCLUSIONS: Disagreement between real-time RT-PCR and immunostaining was demonstrated. Immunostaining seems to be the more reliable method for assessing cyclin E in breast cancer cells.

Adult↗

PubMed2006

Prognostic relevance of basal cytokeratin expression in operable breast cancer.

OBJECTIVE: We investigated whether basal cytokeratin (CK5/6 or CK17) expression had an impact on survival in patients with operable breast cancer. METHODS: Expression of CK5/6 or CK17 was analyzed by immunohistochemistry in 195 women with breast cancer. RESULTS: In total, 72 (37%) tumor samples were regarded as being positive for CK5/6 or CK17. The basal-like phenotype as defined by basal cytokeratin expression, lack of estrogen receptor (ER) and absence of HER2 overexpression was found in 48 (25%) cases. Positive staining for CK5/6 or CK17 was associated with worse prognosis when compared with patients negative for basal cytokeratins in all cases (5-year cancer-specific survival rate 59.4 vs. 77.5%, p = 0.0273) and in the node-negative group (70.5 vs. 90.8%, p = 0.0208) but not in the node-positive group (43.9 vs. 65.4%, p = 0.1182). To determine the real prognostic value of basal cytokeratins, survival in a group of ER-negative patients was analyzed depending on CK5/6 or CK 17 expression. No influence on survival was observed. The outcome of patients whose cancers were positive for cyclin E regardless of ER status was not changed by CK5/6 or CK17 expression. In multivariate analysis, independent prognostic factors affecting survival in the whole group included: nodal involvement, HER2 status and cyclin E expression. Neither ER status nor basal cytokeratin expression retained statistical significance. CONCLUSION: We demonstrated that the poor prognosis associated with the basal-like phenotype of breast cancer was determined by ER absence and cyclin E expression and not by CK5/6 or CK17 expression.

Adult↗

PubMed2005

Effects of anthracycline derivatives on human leukemia K562 cell growth and differentiation.

New derivatives of daunorubicin (DRB), doxorubicin (DOX), and epidoxorubicin (EDOX) with an amidine group bonded to C-3' of daunosamine moiety with either morpholine or hexamethyleneimine ring attached to the amidine group are studied in this paper. We have shown that all of these newly synthesized anthracycline derivatives inhibit human leukemia K562 cell line proliferation but only some of them induce erythroid differentiation when used at subtoxic concentrations. Morpholine derivative of DOX has the greatest potential to inhibit proliferation and to induce differentiation in vitro. The correlation between these two cellular processes was also significant for other tested compounds. In cell cycle analysis, we have demonstrated that those anthracycline derivatives that exert the greatest cytostatic potential caused G(2)/M arrest, which in turn, might contribute to the development of a differentiating phenotype. The concentrations of the compounds used in the study are pharmacologically relevant. These new potent inducers of differentiation might be exploited as anticancer drugs for treatment of leukemia by differentiation therapy.

Anthracyclines↗

PubMed2004

WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins.

WWOX, the gene that maps to common chromosomal fragile site FRA16D, is frequently affected by aberrations in multiple types of cancers. WWOX encodes a 46 kDa protein that contains two WW domains and a short-chain oxidoreductase (SDR) domain. We recently demonstrated that ectopic expression of WWOX inhibits xenograft tumor growth of tumorigenic breast cancer cells. Little is known of the biochemical function(s) of WWOX. The SDR domain is predicted to be involved in sex-steroid metabolism and the WW domains are likely involved in protein-protein interactions. In this report, we identify the specific proline-rich ligand for WWOX as PPXY and show that the amino-terminal WW domain is responsible for this interaction. Using the WWOX WW domains as a probe, we screened high-density protein arrays and identified five candidate-binding partners. The binding to one of these candidates, small membrane protein of the lysosome/late endosome (SIMPLE), was further analysed, and we observed that a specific PPSY motif in the SIMPLE amino-acid sequence was required to interact with the amino-terminal WW domain of WWOX. In addition, immunofluorescence staining demonstrated that endogenous WWOX and SIMPLE co-localize to perinuclear compartments of MCF-7 human breast cancer cells. These studies demonstrate that WWOX contains a Group I WW domain that binds known cellular proteins containing the specific ligand PPXY. Identification and characterization of WWOX interacting proteins will lead to an understanding of the biological functions of WWOX in normal and tumor cells.

Amino Acid Sequence↗