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L Nakopoulou

Publications and source records attributed to L Nakopoulou.

At least 19 recordsLinked to original sources
PubMed2006

Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma.

AIMS: Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. MATERIAL AND METHODS: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed. RESULTS: VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins' expression (p=0.003, p=0.009 and p=0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p=0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients' overall and disease-free survival, respectively (p=0.003 and p=0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p=0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p=0.012 and p=0.038 respectively). CONCLUSION: VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient's poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information.

Adult↗
PubMed2005

PPARgamma expression in breast cancer: clinical value and correlation with ERbeta.

AIMS: To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in invasive breast carcinoma in relation to known clinicopathological features, ERbeta, and relapse-free and overall patient survival. PPARgamma is a ligand-activated transcriptional factor that regulates the transcription of various target genes and has been implicated in human breast cancer. METHODS AND RESULTS: We performed immunohistochemistry to detect PPARgamma, ERalpha, PR and ERbeta in 170 infiltrative breast carcinomas. The results were subjected to statistical analysis. PPARgamma was detected in the cytoplasm of 58% of breast carcinoma samples. PPARgamma did not differ with regard to any of the clinicopathological parameters except for histological grade, to which it was found to be inversely correlated (P = 0.019), and ERbeta, to which it was positively related (P = 0.016). As regards relapse-free survival, in univariate statistical analysis PPARgamma was found to exert a marginally favourable impact on all the patients (P = 0.076), but a strong one on patients with ductal carcinoma (P = 0.027), whereas Cox's regression analysis depicted PPARgamma to be an independent prognosticator for patients with ductal carcinoma (P = 0.039). No association was found between PPARgamma expression and overall survival. CONCLUSION: These results indicate the favourable impact of PPARgamma expression on disease-free survival of patients with ductal breast carcinoma and its possible cooperation with ERbeta in exerting that favourable effect.

Adult↗
PubMed2005

The multifunctional role of the immunohistochemical expression of MMP-7 in invasive breast cancer.

The secretion of matrix metalloproteinases (MMPs) is crucial in the metastasis of cancer cells, since MMPs are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-7 (MMP-7) or matrilysin 1 is a stromelysin which degrades type-IV collagen, fibronectin and laminin. Immunohistochemistry was performed to detect MMP-7 protein in infiltrative breast carcinomas. MMP-7 was studied along with clinicopathological parameters, disease-free and overall survival, and p53, c-erbB-2, topoIIa, MMP-2, uPAR and beta-catenin. MMP-7 immunoreactivity was detected in the cytoplasm of cancer cells in 54.2% (96/177) and tumor stromal cells in 47.5% (84/177), as well as in normal epithelium adjacent to malignant epithelium. MMP-7 reactivity in cancer cells displayed an inverse association with nuclear grade (p=0.049) and topoIIa (p=0.03). A parallel association was observed between the expression of MMP-7 in both malignant and stromal cells with uPAR in cancer cells (p=0.033 and p=0.027, respectively). MMP-7 of tumor stromal cells depicted a parallel correlation with MMP-2 of the same cell type (p=0.044), while abnormal beta-catenin expression was inversely associated with MMP-7 of cancer cells (p=0.047). Our results show the multifunctional role of MMP-7 in the mammary gland, since it seems to be associated with a less aggressive phenotype, while, at the same time, being involved in invasion, through its collaboration with indicators of invasion.

Adult↗
PubMed2005

Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma.

Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients' survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p = 0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p = 0.032) and more often expressed in lobular than ductal carcinomas (p = 0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p = 0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p = 0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.

Adult↗
PubMed2005

Overexpression of cyclooxygenase-2 is associated with a favorable prognostic phenotype in breast carcinoma.

OBJECTIVES: Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients' survival. METHODS: We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. RESULTS: Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p < 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p < 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. CONCLUSIONS: The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARgamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.

Adult↗
PubMed2004

The favourable prognostic value of oestrogen receptor beta immunohistochemical expression in breast cancer.

AIMS: Oestrogen receptor beta (ERbeta) is present in breast tumours, although its prognostic and pathophysiological roles remain to be established. METHODS: Standard immunohistochemistry with a specific monoclonal antibody was performed on paraffin wax embedded sections; 10% of strongly immunostained carcinoma cells was used as the cutoff point to classify tumours as ERbeta positive. Statistical correlations were sought with clinicopathological variables (including hormone receptor status) and disease free (DFS) and overall survival (OS) in a well documented series of 181 invasive breast carcinomas. Cell proliferation was assessed immunohistochemically by topoisomerase IIa (TopoIIa) index; p53 protein accumulation and c-erbB-2 oncoprotein expression were also taken into account. RESULTS: ERbeta immunoreactivity was detected in most specimens (71.2%); it was positively linked to ERalpha immunoreactivity and increased TopoIIalpha index, and inversely to c-erbB-2 overexpression. There were no correlations with p53 immunostaining or other clinicopathological parameters. A significant favourable impact of ERbeta immunopositivity emerged with regard to DFS and OS in both univariate and multivariate analysis; ERbeta immunopositivity retained its favourable significance with regard to DFS in the subgroups of stage I and II patients when they were examined separately. Progesterone receptor expression also had an independent favourable influence on survival, albeit with less significance. In contrast, survival was not significantly influenced by ERalpha status. CONCLUSIONS: Because of the positive association between ERbeta immunoreactivity and TopoIIalpha expression, the presence of ERbeta in breast cancer cells could be considered an indication of increased proliferation. Nevertheless, ERbeta immunoreactivity emerges as a valuable, independent indicator of favourable prognosis.

Adult↗
PubMed2003

Non-endothelial KDR/flk-1 expression is associated with increased survival of patients with urothelial bladder carcinomas.

AIMS: To investigate the immunohistochemical expression of KDR/flk-1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl-2 protein expression and patient survival. KDR/flk-1 is a high-affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk-1 is also expressed by normal non-endothelial and tumour cells. METHODS AND RESULTS: Immunohistochemistry was performed on paraffin sections using monoclonal and polyclonal antibodies. Statistical analysis was univariate (chi2 log rank test) and multivariate (Cox's model). KDR/flk-1 expression was observed in the cytoplasm of cancerous cells in 68.4% of cases. No statistically significant associations were observed between KDR/flk-1 expression and grade or stage of urothelial carcinomas, Ki67, p53 or Bcl-2 expression. In contrast, widespread KDR/flk-1 expression in more than 50% of cancerous cells was associated with increased survival, on univariate and multivariate analysis (P = 0.0119 and P = 0.042, respectively). CONCLUSIONS: Although the biological significance of non-endothelial KDR/flk-1 expression has not yet been elucidated, its association with better patient survival may be related to the failure of non-endothelial KDR/flk-1 to mediate angiogenic and mitogenic effects.

Adult↗
PubMed2003

The favorable prognostic impact of tissue inhibitor of matrix metalloproteinases-1 protein overexpression in breast cancer cells.

The tissue inhibitor of metalloproteinases-1 (TIMP1) inhibits tumor cell invasion and metastasis in experimental models; in addition, TIMP1 is supposed to possess another important function, cell growth promotion. The potential prognostic significance of TIMP1 in breast cancer remains unclear. We evaluated the significance of the immunohistochemical expression of TIMP1 in a well-documented series of 133 infiltrating breast carcinomas by examining any possible statistical association between this expression and numerous clinicopathological parameters as well as patients' disease-free interval. TIMP1 was generally expressed in both stromal and cancer cells in our specimens. TIMP1 was overexpressed in cancer cells of 60.15% of all cases. Tumors of high histological and nuclear grade were found to overexpress TIMP1 less frequently than the rest (p=0.003 and p=0.057, respectively). Interestingly, TIMP1 overexpression was inversely associated with cell proliferation, the latter being evidenced by Ki67 immunoreactivity (p=0.028). TIMP1 immunostaining was in parallel with metalloproteinase-2 (MMP2) immunoexpression in both cancer and stromal cells. Multivariate analysis disclosed that TIMP1 overexpression in cancer cells was an independent determining factor for prognosis (p=0.006); TIMP1 overexpression in malignant cells appeared to correlate with favorable outcome, particularly in patients with lack of nodal metastases and in patients with MMP2-negative immunophenotype (p=0.0252). The upregulation of TIMP1 cancer cell expression in breast cancer may suggest that this marker has a multifunctional role apart from that of metalloproteinase inhibitor since it was found to be related to malignant cells' differentiation and proliferation. TIMP1 overexpression in cancer cells appears for the first time to be a promising indicator of favorable prognosis in breast cancer.

Biomarkers, Tumor↗
PubMed2002

Abnormal alpha-catenin expression in invasive breast cancer correlates with poor patient survival.

AIMS: alpha-Catenin is a member of the E-cadherin-catenin family of adhesion molecules whose role is essential for the function of the E-cadherin complex. In this study, we have evaluated the expression of alpha-catenin but also of the other catenins (beta-, gamma- and p120-catenin) and E-cadherin in invasive breast cancer and statistically analysed these expressions with known clinicopathological parameters, c-erbB-2 oncoprotein expression and patient survival. METHODS AND RESULTS: Abnormal E-cadherin and beta-catenin expression, especially loss of expression, was associated with lobular histological type of breast carcinomas (P=0.03 and P=0.01, respectively). Abnormal E-cadherin and alpha-catenin expression was associated with high histological grade ductal carcinomas (P=0.01 and P=0.03, respectively). Abnormal E-cadherin and beta-catenin expression was correlated with lymph node metastases (P=0.02 and P=0.05, respectively), while abnormal alpha- and beta-catenin were correlated with the advanced stage of the disease (P=0.04 and P=0.05, respectively). Abnormal p120-catenin expression was associated with loss of PR (P=0.008). Survival analysis demonstrated a statistically significant association between abnormal alpha-catenin expression and poor patient survival (P=0.02). When survival analysis was performed according to the different patterns of abnormal expression, statistically significant associations were seen between cytoplasmic alpha- and beta-catenin expression and poor survival (P=0.006 and P=0.04, respectively). CONCLUSIONS: alpha-Catenin, especially its cytoplasmic expression, seems to be a more sensitive prognostic marker than the other members of the E-cadherin complex in invasive breast cancer.

Adult↗
PubMed2002

Diagnostic approach of effusion cytology using computerized image analysis.

The objective of this study is to investigate whether image cytometry is a sensitive and specific method for the differential diagnosis of equivocal cells in routine cytology of effusion smears. One hundred four effusion smears were studied from routine cytologic material. Cytologically 56 (53.8%) of the smears were classified as malignant, 26 (24%) as suspicious and 22 (21.1%) as benign. Two morphometric variables (nuclear major axis length and nuclear area) of the nuclei were measured by an image analysis system. Higher values for the area were found for malignant rather than benign and suspicious cells (p < 0.0005 and p < 0.005 respectively). The same result was extracted for the nuclear major axis length values (p < 0.0005 and p < 0.0005 respectively). Values of nuclear major axis length and nuclear area didn't differ significantly between benign and suspicious cells (p = 0.071 and p = 0.066 respectively). The results show that the range of the values for suspicious cells is closer to the range of the benign cells. Cytomorphometry of the effusion smear cells may provide important information for the differentiation of atypical mesothelial cells from malignant adenocarcinoma cells.

Adenocarcinoma↗
PubMed2001

Glomerulopathy with mesangial IgM deposits: long-term follow up of 64 children.

BACKGROUND: The aim of the present study was to investigate to what extent IgM nephropathy in children with minimal change nephrotic syndrome (MCNS) and diffuse mesangial hypercellularity (DMH) evolves to focal segmental glomerulosclerosis (FSGS). METHODS: Tissues from renal biopsies were examined by light microscopy (LM), immunofluorescence (IF) and, in four cases, by electron microscopy (EM). From a total of 352 nephrotic children, 121 had renal biopsy results as steroid dependent or resistant. A diagnostic renal biopsy was also performed in 331 children with non-nephrotic proteinuria and/or hematuria. A second renal biopsy was performed in 16 children whose renal function was impaired during the follow up. The clinical course of IgM-positive children was compared with that of IgM-negative children. RESULTS: Of the 121 nephrotic children with renal biopsy, 85 were MCNS. Twenty were IF positive mainly for IgM, six of whom (30%) presented evolution to FSGS, while of the remaining 65 IF-negative children, only three (4.6%) presented evolution to FSGS. Of the total 331 children with non-nephrotic proteinuria and/or hematuria, 139 were diagnosed as IgA--IgG nephropathy, 44 had positive IF for IgM and 148 were IF negative. Of the 44 children IF positive for IgM, seven (15.9%) presented evolution to FSGS, while none of the 148 IF-negative children presented evolution to FSGS. The follow-up time for all children ranged from 1 to 14 years. CONCLUSIONS: Of IgM nephropathy patients with MCNS and DMH, a significant percentage develop impaired renal function, due to the evolution of FSGS, as revealed by repeat biopsy during long-term follow up.

Adolescent↗
PubMed2001

Expression patterns of beta-catenin in in situ and invasive breast cancer.

BACKGROUND: beta-Catenin plays a central role in the E-cadherin/catenin cell-cell adhesion complex and is possibly involved in cellular signalling pathways. In this study, we evaluated the expression patterns of this molecule in in situ and invasive breast cancer. METHODS: The expression of beta-catenin was evaluated in 121 breast cancer specimens by immunohistochemistry. Its relationship to clinicopathological features was also investigated. RESULTS: Altered beta-catenin expression was found in 68% of tumours. Lobular carcinomas showed abnormal beta-catenin expression more frequently (77%) than ductal carcinomas (64%) with 46% of lobular cases showing complete absence of beta-catenin immunoreactivity. Cytoplasmic beta-catenin localization was seen only in ductal carcinomas. Aberrant beta-catenin expression was observed in 54% of ductal carcinomas in situ with highly concordant beta-catenin expression patterns in the nearby in situ and invasive components. CONCLUSIONS: Quantitative and qualitative changes in beta-catenin expression occur in a considerable proportion of in situ and invasive ductal carcinomas and are more prominent in invasive lobular carcinomas.

Adult↗
PubMed2001

MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: a comparison with clinicopathologic features and survival.

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients' disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients' disease-free and overall survival. In conclusion, the authors' results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.

Adult↗
PubMed2001

Predictive value of topoisomerase II alpha immunostaining in urothelial bladder carcinoma.

AIMS: The nuclear enzyme DNA topoisomerase II has been shown to be required for chromatin condensation and chromosomal segregation during mitosis; its isoform topo II alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relation of the expression of topo II alpha to the biological behaviour of conventional urinary bladder cancer. METHODS: Formalin fixed, paraffin wax embedded tissue from 94 specimens of bladder urothelial cancer were immuno-histochemically stained for topo II alpha. For each case, a topo II alpha index was determined. A similar index had been determined for Ki-67, a known cell proliferation marker. Each case had also been graded, staged, and evaluated for DNA ploidy as well as for p53 and bcl-2 immunoreactivity. RESULTS: Raised topo II alpha expression (in > or = 10% of malignant nuclei) correlated with two adverse prognosticators--high grade (p = 0.027) and invasion of the muscularis propria (p = 0.013), but with no other evaluated parameter. By multivariate survival analysis using Cox's proportional hazard model, high expression of topo II alpha was found to be predictive for worse survival (p = 0.0047). Patients' age, tumour stage, and grade were also retained as independent prognostic factors (p = 0.0349, p = 0.00005, and p = 0.0130, respectively). The negative influence of increased topo II alpha immunopositivity on patients' survival was also seen in the subgroup of patients with non-muscle invasive carcinomas (p = 0.0004), in patients with a bcl-2 negative phenotype (p = 0.0330), and in those with low Ki-67 indices (p = 0.0341). CONCLUSIONS: Because topo II alpha and Ki-67 failed to demonstrate a significant interrelation, they appear to be different molecules that both function at separate phases in the complex process of cellular proliferation. The assessment of increased topo II alpha immunoreactivity in specimens from urothelial carcinomas might help to select patients (particularly among those with superficial tumours) in the worse prognostic categories for new therapeutic strategies.

Carcinoma, Transitional Cell↗
PubMed2001

Immunohistochemical expression of caspase-3 as an adverse indicator of the clinical outcome in human breast cancer.

OBJECTIVE: Tumor growth is the net result of cell proliferation and cell loss by apoptosis. Caspase-3 (CPP32) has been considered as most directly correlated with apoptosis because of its location in the protease cascade pathway. The aim of this study was to examine the relation of the immunohistochemical expression of caspase-3 in 137 infiltrating breast carcinomas to patients' clinicopathological parameters and survival. METHOD: A polyclonal antibody against caspase-3 was applied using a standard immunohistochemical procedure to paraffin sections. RESULTS: By comparison with nonneoplastic breast tissue, caspase-3 appeared to be upregulated in malignant breast tissue, and its overexpression status was detected in 75.2% of the specimens. Significant statistical correlations were observed between overexpression of caspase-3 and low nuclear grade (p = 0.048), lack of p53 protein accumulation (p = 0.039), bcl-2-positive immunostaining (p = 0.027), as well as tissue inhibitor of metalloproteinase-2 immunoreactivity of neoplastic (p = 0.012) and stromal cells (p = 0.0001). Despite the above correlations, multivariate analysis revealed a significant negative influence of caspase-3 expression on patients' overall survival (p = 0.029). CONCLUSIONS: Caspase-3 protein overexpression appears to be involved in the apoptotic pathways influenced by wild-type p53 and bcl-2 proteins. Moreover, the results show that caspase-3 overexpression in breast cancer cells seems to exert an independent adverse effect on patients' overall survival.

Adult↗