ABSTRACT
Fas and its ligand (FasL) are known to play a crucial role in the genetically controlled mechanism of cell death, and their deregulation in cancer cells is involved in the immune escape of the tumor. The aim of this review is to analyze the current knowledge on the prognostic value of Fas/FasL in breast cancer patients. Both the results of other authors and our own experiences indicate that the lack of Fas ligand, and particularly Fas, is related to a significantly worse prognosis. It probably results from the resistance of Fas-deficient breast tumors to the mechanisms of apoptosis. On the other hand, some results suggest that the Fas/FasL-dependent mechanisms of tumor spread may be different for various target tissues. The expression of the Fas/Fas-ligand system has potential prognostic application in view of current knowledge, and consequently should be considered as an additional prognostic factor in breast cancer patients.
ABSTRACT
UNLABELLED: The aim of the study was to evaluate the prognostic value of vascular endothelial growth factor C (VEGF-C) and VEGF-D expression in stage II, grade 2 and 3, ductal breast cancer patients. PATIENTS AND METHODS: The immunohistochemical staining of 98 tumor samples and 5- and 10-year overall (OS) and disease-free survival (DFS) were analyzed. RESULTS: A significant relationship between VEGF-C and VEGF-D expression (p=0.000002) was noted. No correlations between protein expression and clinical parameters (tumor size, grade, estrogen receptor status, axillaty lymph node metastases and age) or 5- and 10-year DFS or OS were demonstrated. A close to significant correlation (p=0.084) was observed between high expression of VEGF-C and 5-year OS. CONCLUSION: Our study did not reveal any prognostic value of VEGF-C or VEGF-D. Therefore they are not useful as markers for patients with poor prognosis. Unlike in other studies, our patient group was homogenous which might have contributed to the results obtained.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Vascular Endothelial Growth Factor C/biosynthesis , Vascular Endothelial Growth Factor D/biosynthesis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Immunohistochemistry , Middle Aged , Neoplasm StagingABSTRACT
BACKGROUND: Bones belong to the most frequent localizations of breast cancer metastases. Several studies on female breast malignancies have indicated that Fas/Fas-ligand status may have a significant impact on survival. Hence, the aim of our study was to determine if these molecules might serve as the predictors of skeletal dissemination in radically-treated breast cancer patients. PATIENTS AND METHODS: Tumor samples from 147 radically-treated breast cancer patients were studied immunohistochemically for Fas/Fas-ligand expression. RESULTS: Both Fas and Fas-ligand expression in the primary tumor were considerably less frequent among breast cancer patients with bone metastases compared to women without skeletal spread. Moreover, negative staining for Fas or the lack of Fas-ligand expression proved to be significant predictors for the survival free from bone metastases under univariate analysis. CONCLUSION: Our results suggest that the probability of bone metastases may be assessed on the basis of Fas/Fas-ligand expression in primary breast cancer. Consequently, their determination seems crucial for further prognosis and determination of adjuvant treatment.
Subject(s)
Bone Neoplasms/secondary , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Fas Ligand Protein/biosynthesis , fas Receptor/biosynthesis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Predictive Value of Tests , Risk FactorsABSTRACT
BACKGROUND: Several studies on breast cancer patients indicate that Fas/FasL status may have a significant impact on patient survival, but their conclusions are still controversial. The aim of this study was to determine the prognostic value of Fas and Fas ligand (FasL) expressions in the early stages of breast cancer. MATERIAL/METHODS: One hundred and eight patients aged 35-77 years (median: 58), mostly with stage I or II tumors, were analyzed. RESULTS: Significant associations were noted between Fas expression and lymph node involvement (p<0.0001) or the number of recurrences (p=0.02) and between the presence of FasL and the histological grade of tumor (p=0.007). A five-year follow-up was available for 80/108 (84%) patients: 52/66 (79%) with Fas-positive and 28/42 (67%) with Fas-negative tumors (p=0.102). Considering the expression of FasL, 31/45 (69%) patients with positive and 50/63 (79%) with negative immunostaining have survived five years following surgery (p=0.157). CONCLUSIONS: The study demonstrated that the components of the Fas/FasL system are associated with the clinical outcome of breast cancer and consequently should be considered in prognosis, complementing the existing conventional factors.
Subject(s)
Breast Neoplasms/diagnosis , Carcinoma/diagnosis , Fas Ligand Protein/biosynthesis , Gene Expression Regulation, Neoplastic , Prognosis , fas Receptor/biosynthesis , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma/metabolism , Carcinoma/pathology , Female , Humans , Lymphatic Metastasis , Middle Aged , Phenotype , Receptors, Estrogen/metabolism , Time FactorsABSTRACT
The choice of cell lines for multidrug resistance (MDR) modulators screening may affect the results obtained. Screening is most often performed in model systems which employ cell lines derived from haematological malignancies. Cell lines originating from solid tumours are far less popular. In the present work, we aimed to test the usefulness of the drug-sensitive human sarcoma cell line MES-SA, and its multidrug-resistant counterpart MES-SA/Dx5, as a model system for modulators' anti-MDR potency evaluation. Overexpression of P-glycoprotein in the resistant but not in the sensitive cell line was confirmed by flow cytometry and confocal microscopy. Flow cytometry demonstrated that verapamil and trifluoperazine reduced MDR in MES-SA/Dx5 cells as assessed by the rhodamine 123 accumulation test. Both modulators also restored in MES-SA/Dx5 cells the drug accumulation pattern typical for sensitive cells, as judged by confocal microscopy. We conclude that the MES-SA and MES-SA/Dx5 cell line pair constitute a good model for MDR modulators study.
Subject(s)
Cell Line, Tumor , Drug Resistance, Multiple , Sarcoma/drug therapy , Uterine Neoplasms/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Drug Resistance, Neoplasm , Female , Flow Cytometry , Humans , Rhodamine 123/pharmacokinetics , Sarcoma/metabolism , Sarcoma/pathology , Uterine Neoplasms/metabolism , Uterine Neoplasms/pathologyABSTRACT
OBJECTIVE: the aim of our study was determination of the relationship between angiogenesis and clinical as well as histological features in laryngeal cancer. METHODS: we used two different methods of estimation of the amount of microvessels in the series of 55 cases, e.g. classical count of endothelial cells group (h-MVD) and digital image measurement of the vessel density (VD). RESULTS: neither h-MVD nor VD correlated significantly with clinical features of the tumour. The results of VD examination correlated significantly with the existence of nodal metastases (P=0.02). The relationship between h-MVD and N status was on the statistical borderline (P=0.07). Multivariate analysis of Cox's proportional hazards model revealed that only N status correlated significantly with patients' survival. CONCLUSION: our results indicate that measurements of angiogenesis in laryngeal cancer may be of some value in predicting N status in laryngeal cancer patients. This issue should be confirmed in prospective studies.
