Biomedical subjects

I Giannopoulou

Publications and source records attributed to I Giannopoulou.

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↗

PubMed2006

Regional differences in abdominal fat loss.

OBJECTIVE: This study determined if the magnetic resonance imaging (MRI) protocol used alters the estimation of change in abdominal fat with weight loss in obese type 2 diabetic women. This study also examined if there is a uniform fat loss across the abdomen. METHODS AND PROCEDURES: Thirty-three obese postmenopausal women with type 2 diabetes (age 50-70 years, body mass index>30 kg/m(2)) had a total abdominal MRI scan pre- and post weight loss intervention. Three different MRI analysis protocols were used and compared: a single slice at L(2)-L(3) vs five slices (centered at L(4)-L(5)) vs all abdominal slices. In addition, the total abdominal scan was divided into four regions (four slices each) with region 3 (critical region) including the traditionally studied L(2)-L(3), and regions 1 and 2 superior and region 4 inferior to critical region 3. Analysis of variance (ANOVA) with repeated measures was used to compare the influence of weight loss on abdominal fat measured both regionally and using the varying number of MR slices. RESULTS: At baseline, the ratio of visceral adipose tissue:subcutaneous adipose tissue (VAT:SAT) was significantly lower using the single-slice method compared to five slices and the total abdomen (P<0.01). Using the single-slice method, a lower %VAT was found than with the other methods (P<0.01). In regions 1, 2, 3, and 4, the absolute change in total fat was 122+/-50, 182+/-48, 182+/-55, and 155+/-40 cm(3), respectively. The regional difference in abdominal fat patterning revealed that the critical region (region 3) had a smaller VAT:SAT ratio than regions 1 and 2 (P<0.05), and the ratio at region 4 was smaller than region 3 (P<0.05). Weight loss resulted in a decrease in the VAT:SAT ratio (P<0.05) for regions 3 and 4 but not for regions 1 and 2. CONCLUSIONS: The number of MR slices analyzed yields differential result in relative VAT distribution. Regional differences in abdominal fat loss occur with a greater relative VAT loss in the critical region, thus if only the critical region is analyzed the overall VAT loss induced by weight loss intervention may be overestimated.

Abdominal Fat↗

PubMed2006

Study of phospho-beta-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome.

Beta-catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated beta-catenin, as well as its relation to the tumors' phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-beta-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-beta-catenin index was determined by image analysis. Phospho-beta-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-beta-catenin was statistically higher in carcinomas of smaller tumor size (P = 0.030), lower stage (P = 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P = 0.052 and P = 0.037, respectively). Nuclear phospho-beta-catenin showed a parallel correlation with ER and ERbeta (P = 0.022 and P = 0.043, respectively), bcl-2 (P = 0.042), uPAR in cancer cells (P = 0.041) and TIMP-1, although the correlation was borderline (P = 0.066). Cytoplasmic phospho-beta-catenin was found to be independently correlated with prolonged disease-free and overall survival (P = 0.046 and P = 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P = 0.046). In conclusion, phospho-beta-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients' overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.

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

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↗

PubMed2005

Hormone-replacement therapy use, but not race, impacts the resting and exercise-induced GH response in postmenopausal women.

OBJECTIVE: This study examined the effect of hormone-replacement therapy (HRT) use on the incremental GH response to aerobic exercise in postmenopausal women and established whether racial differences in the GH response were seen at rest and in response to exercise. METHODS: 13 white (n = 6, HRT; n = 7, no HRT) and seven black women (no HRT) were studied on two occasions, a control day and an exercise day (30 min at 70% VO(2)max on a cycle ergometer). Blood was sampled every 10 min for a 4-h period and analyzed for GH using an ultrasensitive chemiluminescent assay. RESULTS: The mean 4-h GH concentration was higher on both study days in the HRT women than the non-HRT users. The integrated GH concentrations were greater in the HRT women both at rest and in response to exercise (rest, 352 +/- 53 min microg l(-1); exercise, 711 +/- 57 min microg l(-1); P < 0.01) than in the non-HRT women (rest, 157 +/- 87 min microg l(-1); exercise, 248 +/- 94 min microg l(-1)). The incremental GH response was greater in the HRT users than in the non-HRT women (358 +/- 130 versus 90.8 +/- 94 min microg l(-1), respectively; P < 0.05). GH-production rate during the 4-h period was greater in the HRT women than in the non-HRT women (P < 0.01), due to an increase in the GH mass secreted/pulse (P < 0.05), with no change in GH pulse number or GH half-life. No racial differences in the mean 4-h GH concentrations or integrated GH concentrations were found at rest or in response to exercise. CONCLUSION: HRT use resulted in a greater incremental exercise response compared with non-HRT users, due to changes in the secretory pulse characteristics in the HRT users. This study also demonstrated that no racial differences exist at rest and in response to exercise in the morning hours.

Bicycling↗

PubMed2004

Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes.

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight ( approximately 4.5 kg) and percent body fat ( approximately 5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat ( approximately 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.

Adipose Tissue↗

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

Adrenocortical responses to submaximal exercise in postmenopausal black and white women.

The purpose of this study was to determine whether racial differences exist in the dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and cortisol concentrations of black and white postmenopausal women at rest and in response to submaximal exercise. Twenty-three postmenopausal women (13 white and 10 black) were studied on 2 occasions. On one occasion subjects rested quietly for 4 hours (control day), whereas on the other occasion after 50 minutes of rest, subjects exercised at 70% of Vo(2) peak for 30 minutes on a cycle ergometer (exercise day). Blood was sampled at rest, during exercise, and during recovery and assayed for DHEA, DHEAS, and cortisol concentrations. Resting DHEA and cortisol concentrations and integrated area under the curve (AUC) were similar between the black and white women; however, the black women had lower resting DHEAS concentrations compared with the white women (DHEAS, black: 1.32 +/- 0.29 v white: 2.18 +/- 0.25 micromol. L(-1), P <.05). Regardless of race, DHEA and cortisol AUC increased significantly above resting values (P <.01), but the exercise AUC for DHEA and cortisol were not different between the black and white women (DHEA: 607 +/- 133 and 824 +/- 108 min x nmol. L(-1); cortisol: 9,604 +/- 1,247 and 8,076 +/- 1,093 min x nmol. L(-1), respectively). No exercise-induced change in integrated DHEAS AUC was found in either group. In conclusion, racial differences exist in the resting DHEAS levels of postmenopausal women, but with no racial differences in resting DHEA and cortisol concentrations. Race had no impact on these adrenal hormone responses to submaximal exercise.

Adipose Tissue↗

PubMed2003

Racial differences in subcutaneous and visceral fat distribution in postmenopausal black and white women.

Most studies examining racial disparities in abdominal fat distribution have focused on premenopausal women. The purpose of this report was to determine if racial differences exist in the abdominal fat distribution in postmenopausal white and black women. Fifty-four women (33 white and 21 black) were scanned by magnetic resonance imaging (MRI) to determine abdominal fat distribution, were measured by hydrostatic weighing for percent body fat, and had their fasting blood lipids, glucose, and insulin levels measured. These women were matched for age (mean age, 53.5 +/- 0.9 years) and percent body fat (black: 39.6% +/- 2.3%, white: 37.3% +/- 1.2%). When adjusted for total body fat mass and hormone replacement therapy (HRT), total abdominal fat (white: 10,352.1 +/- 535.2, black: 11,220.4 +/- 670.1 cm(3)) was not statistically different between groups, but the visceral fat content was significantly higher in the white women (white: 2,943.5 +/- 220.4, black: 2,332.6 +/- 176.1 cm(3)). The percent visceral fat was also higher in these women (white: 30.5% +/- 1.3%, black: 22.1% +/- 1.6%, P <.01). Subcutaneous adipose tissue (SAT) was significantly higher in the black women (white: 7,408.6 +/- 450.2, black: 8,887 +/- 563.1 cm(3), P <.05). No significant differences were found in the insulin concentrations or the blood lipid profile of these women. Regardless of race, visceral fat was a significant predictor of log triglyceride, low-density lipoprotein-cholesterol (LDL-C), cholesterol/LDL-C, insulin levels, and insulin resistance. Race was only found to contribute to 8% of the variability of LDL-C. HRT use had no effect on abdominal fat distribution or the blood lipid profile in this cohort of women. In conclusion, disparities in abdominal fat distribution between black and white women continue to exist in the early postmenopausal years, and the regression results indicate that the absolute amount of visceral fat, and not the relative amounts of visceral fat, is the best predictor of the blood lipid profile and insulin sensitivity. HRT use did not result in differences in abdominal fat distribution in these women. Factors, such as genetics and lifestyle, must play a larger role in explaining the increased health risk in black women.

Abdomen↗

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↗

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↗

PubMed2000

c-met tyrosine kinase receptor expression is associated with abnormal beta-catenin expression and favourable prognostic factors in invasive breast carcinoma.

AIMS: Receptor-type tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. c-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). In this study, we have evaluated c-met expression in 69 invasive breast carcinomas and statistically analysed this expression with known clinicopathological prognostic parameters and patients' survival. We also studied for the first time c-met expression in association with E-cadherin and beta-catenin expression. METHODS AND RESULTS: Immunohistochemistry (ABC-HRP method) was peformed for the detection of c-met, E-cadherin and beta-catenin. c-met immunoreactivity was observed in 58% of cases and was associated with the lobular type of breast carcinomas (P = 0.012), low histological grade ductal carcinomas (P = 0.05), favourable prognostic and predictive factors such as oestrogen and progesterone receptor immunohistochemical expression and negative c-erbB-2 expression (P = 0.05, P = 0.014 and P = 0.03, respectively). c-met immunoreactivity did not correlate with lymph node status, tumour size and stage of the disease. Cox's proportional hazard regression model demonstrated that tumours with positive c-met immunoreactivity correlated significantly with favourable patients' survival (P = 0.028). When c-met staining was compared with E-cadherin and beta-catenin expression, a statistical significant correlation was established between c-met immunoreactivity and abnormal beta-catenin expression (P = 0.025) suggesting possible involvement of c-met in the downregulation of the E-cadherin-catenin complex, possibly through tyrosine phosphorylation of beta-catenin. CONCLUSION: c-met immunohistochemical expression seems to be associated with abnormal beta-catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.

Adult↗

PubMed1999

Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features.

Although matrix metalloproteinases (MMPs) are implicated in breast cancer progression, the contribution of MMP-1 and MMP-3 to this process, has not been thoroughly investigated. Matrix metalloproteinases (MMPs) are important at several points during multistage neoplastic progression. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1, MMM-3 proteins, and MMP-3 mRNA, respectively, in 77 infiltrative breast carcinomas. MMP-1, MMP-3 protein, and MMP-3 mRNA detection were analyzed in parallel with clinicopathologic features (menopausal status, histological type, nuclear and histological grade, stage) and the immunohistochemical reactivity of estrogen (ER), progesterone (PR) receptors, and c-erbB-2 oncoprotein in breast carcinomas. Statistical analysis was performed using the multiple linear regression test. Immunoreactivity for MMP-1 and MMP-3 was observed in 59 of 77 (77%) and 22 of 77 (28.5%) breast carcinomas and was evaluated separately in cancer cells and in stromal fibroblasts. MMP-3 mRNA was detected in 72 of 77 (93.5%) carcinomas exclusively in stromal cells within the tumors or in the marginal portion of tumors. MMP-1 protein immunoreactivity in stromal fibroblasts but not in cancer cells showed a statistically significant correlation with tumor stage (P=.04). MMP-1 reactivity either in stromal or in cancer cells showed a statistically significant inverse correlation with PR expression (P=.04 and P=.04, respectively). MMP-3 protein immunoreactivity in cancer or stromal cells and MMP-3 mRNA expression was not associated with the clinicopathologic features studied. MMP-3 mRNA was detected more often in ductal carcinomas. These results indicate that MMP-1 may contribute to breast cancer invasiveness. Furthermore, they suggest differential functions for MMP-1 and MMP-3 in breast cancer progression.

Adult↗

PubMed1999

bcl-2 protein expression is associated with a prognostically favourable phenotype in breast cancer irrespective of p53 immunostaining.

AIM: A role for altered programmed cell death in cancer stems from the description of alterations on tumour-associated genes involved in the regulation of apoptosis such as p53 and bcl-2. The balance between the latter may have significant implications for the pathobiology of breast cancer. This study was therefore undertaken to evaluate the expression of these two gene products with opposite functions. METHODS AND RESULTS: A total of 142 paraffin-embedded tumour blocks were evaluated for nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 immunohistochemistry. The results were semiquantitated. The bcl-2 protein was found within the infiltrating neoplastic cells of 97 (68%) specimens but it was also detectable in tumours' in situ compartments and in benign mammary tissue. We identified a strong correlation between bcl-2 immunoreactivity and oestrogen receptor positivity (P = 0.03), while bcl-2 expression also correlated significantly with small tumour size (P = 0.006) and low nuclear grade (P = 0.01), but it did not correlate with the expression of p53. bcl-2 presence tended to diminish with disease progression (P = 0.06). Quantitatively increased bcl-2 immunostaining was significantly associated with older patients (P = 0.02) as well as with presence of progesterone receptors (P = 0.01). Thirty-seven tumours (26%) were judged positive for p53 protein expression. The p53 positivity status was independent of all classical histopathological variables; however, high p53 expression was negatively linked to oestrogen receptors (P = 0.005). CONCLUSION: In breast cancer, bcl-2 protein is associated with a prognostically favourable phenotype and appears to be related to hormonal regulation, rather than to disabled p53 gene function.

Adult↗

PubMed1995

Prognostic evaluation of oestrogen-regulated protein immunoreactivity in ductal invasive (NOS) breast cancer.

Determination of steroid receptors and several oestrogen-regulated proteins in mammary carcinomas is useful in the prediction of their evolution and of the likely success of endocrine therapy. Cathepsin D (Cat D), pS2 peptide and heat shock protein 27 (Hsp 27) were detected immunohistochemically in 63 infiltrating ductal (NOS) breast carcinomas, and our results were qualitatively correlated with several clinicopathological indicators and patients' overall survival. Cat D immunostaining of tumour cells was strongly associated with axillary nodal involvement (Pf = 0.0005) and so, it is directly connected with the metastatic capacity of malignant cells. pS2 immunoreactivity was correlated with oestrogen and progesterone receptor positivity (Pf = 0.0009 and Pf = 0.05 respectively) and, nonsignificantly, with good differentiation of the tumours (Pf = 0.06). Neoplastic cells expressing this protein are therefore characterised by a highly organised state of cellular physiology. Hsp 27 was expressed predominantly in tumours with one to four infiltrated lymph nodes (Pt = 0.05), and Hsp 27-positive patients were inclined to rather short survival, possibly due to chemotherapy resistance. In future, prognostic estimation of each one of the examined markers should be performed in specific large subgroups of patients. The findings of this study contribute to the establishment of criteria by which these subgroups should be formed.

Adult↗