PubMed Health⌕ Search

Biomedical subjects

Andreas C Lazaris

Publications and source records attributed to Andreas C Lazaris.

At least 19 recordsLinked to original sources
PubMed2006

The expression of matrix metalloproteinase-11 protein in various types of glomerulonephritis.

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated to play important roles in a number of pathological processes such as inflammation. In human glomeruli, the mesangial matrix turnover is controlled by a dynamic equilibrium between synthesis and degradation to which metalloproteinases are known to contribute. Metalloproteinase-11 (MMP-11) was originally discovered as a gene whose expression was associated with tissue remodelling. The aim of this study was to investigate whether MMP-11 protein is expressed in various types of glomerulonephritis and to elucidate the role of this expression. METHODS: Using standard immunohistochemistry, we analysed MMP-11 expression in renal biopsies from 95 patients with primary glomerulonephritis (n = 44) and secondary, either lupus-associated glomerulonephritis (n = 22) or pauci-immune, ANCA-associated glomerulonephritis due to small vessel vasculitis (n = 23) or Wegener's granulomatosis (n = 6). The examined cases were divided into two groups (proliferative and non-proliferative). Anti-Ki67 and -CD68 immunostaining was also performed in order to estimate cell proliferation and number of macrophages, respectively. RESULTS: MMP-11 immunopositivity was detected in the glomeruli of the majority of pathological samples. The highest incidence of MMP-11 immunopositivity (26.3%) was noticed in glomerulonephritides associated with microscopic polyangiitis and Wegener's granulomatosis. Generally, MMP-11 was often expressed in segmental areas of sclerosis, microadhesions, cellular and fibrocellular crescents. Fibrotic crescents and fibrotic glomeruli were constantly MMP-11-immunonegative. In MMP-11 immunoreactive glomeruli, increased numbers of macrophages were often detected in the mesangium (P = 0.001), while no such observation could be made with regard to proliferating cells (P = 0.170). CONCLUSIONS: MMP-11, like an inflammatory mediator, may exert a chemotactic influence on macrophages which aggregate in the mesangium; MMP-11 is not likely to have a parallel mitogenic or antifibrotic effect in diseased glomeruli.

Antigens, CD↗
PubMed2006

Expression of ets-1 is not affected by N-ras or H-ras during oral oncogenesis.

PURPOSE: To determine whether ras-activated cascades lead to activation of ets-1 expression in sequential histological stages of oral oncogenesis in an experimental animal model. METHODS: Thirty-seven Syrian golden hamsters were divided into three experimental groups (A, B, C) and one control group. The hamsters' buccal pouches in experimental groups were treated with 0.5% 9, 10-dimethyl-1, 2-benzanthracene (DMBA) for 14 weeks and were excised at 10, 14, 19 weeks, respectively. The biopsies were classified pathologically (normal mucosa, hyperkeratosis, hyperplasia, dysplasia, early invasion, well and moderately differentiated carcinoma) and studied immunohistochemically. The two-tailed Student's t test was performed for each animal group and for each histological category. RESULTS: The ets-1 expression increased in early stages of oral tumor formation and invasion. The expression of N-ras gradually decreased during oral oncogenesis, as previously observed with H-ras. CONCLUSIONS: Neither N-ras nor H-ras affects ets-1 expression in contrast to other types of cancer in which N-ras and ets-1 are implicated in the same signalling pathway. Therefore, the existing pathway implicating these proteins might be somehow altered in oral cancer. It seems that ets-1 is a good prognostic marker for invasiveness and progression of oral cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

Cytokeratin-7, cytokeratin-19, and c-Kit: Immunoreaction during the evolution stages of primary biliary cirrhosis.

AIMS: The quantitative and qualitative expression of CK-7, CK-19, and c-Kit markers in various cell types were evaluated during the four stages of primary biliary cirrhosis. METHODS: A total of 53 specimens were examined. Thirteen specimens were identified as Ludwig's stage 1, 23 as stage 2, 14 as stage 3, and 2 as stage 4. Immunohistochemical stains were performed for CK-7, CK-19, c-Kit and subsequently graded. The cell types expressing the markers were qualitatively analysed. RESULTS: In normal liver, biliary epithelial cells expressed CK-7, CK-19, whereas the Canals of Hering (CoH) were stained with c-Kit and partly CK-19, contrary to hepatocytes. The aforementioned expression patterns were detected in pathologic samples of PBC, with qualitative and quantitative differences though. CK-7 grading was found to correspond with Ludwig's staging, in contrast to CK-19. c-Kit was absent in the early stages and focally present in the advanced stages. All biliary-type, intermediate cells and hepatocytes were CK-7 positive, particularly in samples with cholestasis, whereas CK-19 was only found in biliary-type and intermediate cells. c-Kit was expressed in CoH which appeared as clusters and strings of cuboidal cells in advanced stages. CONCLUSIONS: CK-7 can be regarded as a histological marker of progression in PBC; CK-19 cannot be assessed as a safe marker in the development of the disease. The absence of c-Kit in the early stages of PBC is related to the destruction of the CoH. CK-7 hepatocyte expression in the advanced stages is likely to be related to damaged hepatocytes' metaplastic potential.

Journal Article↗
PubMed2006

Primary diffuse large B-cell lymphoma of the skin.

B-cell lymphomas of the skin represent a wide spectrum of disorders. We present the microscopic and immunohistochemical features of a primary cutaneous B-cell lymphoma and classify it either as a diffuse large B-cell lymphoma or an indolent follicle-center-cell lymphoma according to the updated REAL/WHO system and the EORTC classification respectively. The former system is widely recommended; nevertheless, the EORTC system is also worth considering when planning management, because most data on long-term outcomes are based on it and it is considered to offer remarkable prognostic information.

Antigens, CD20↗
PubMed2006

HER2/neu expression and gene alterations in pancreatic ductal adenocarcinoma: a comparative immunohistochemistry and chromogenic in situ hybridization study based on tissue microarrays and computerized image analysis.

CONTEXT: HER2/neu overexpression is observed in many cancers including pancreatic ductal adenocarcinoma. Although immunohistochemistry remains the basic method for evaluating HER2/neu protein expression, significant information regarding gene status cannot be assessed. DESIGN: Using tissue microarray technology, fifty histologically confirmed pancreatic ductal adenocarcinomas were cored twice and re-embedded in one paraffin block. Immunohistochemistry (clone TAB 250) and chromogenic (HER2/neu amplification Spot Light kit) in situ hybridization protocols were performed. The immunostained slides were evaluated by conventional eye microscopy and digital image analysis. The chi square test and the kappa statistic were applied by running the SPSS package. MAIN OUTCOME MEASURES: The levels of staining intensity were estimated by the performance of a semi automated image analysis system. RESULTS: HER2/neu gene amplification was detected in 8/50 cases (16%). Chromosome 17 aneuploidy was detected in 19 cases (38%). Significant improvement in interobserver agreement (kappa=0.76 vs. 0.94) was achieved correlating the immunohistochemical results obtained by conventional eye and digital microscopy, especially in the cases of overexpression (2+, 3+). Finally, 29 (58%), 11 (22%), 6 (12%) and 4 (8%) cases were characterized as 0, 1+, 2+ and 3+, respectively. HER2/neu protein expression was significantly associated with grade (P=0.019), but not with stage (P=0.466). in addition, chromosome 17 and gene status were not correlated with stage and grade. CONCLUSION: Our results indicate that a subset of pancreatic ductal adenocarcinomas is characterized by HER2/neu gene amplification. In contrast to breast cancer, protein overexpression does not predict this specific gene deregulation mechanism. This event may reflect the different biological role of the molecule in those two solid tumours, affecting the response to novel targeted agents, such as monoclonal anti-HER2/neu antibodies. Furthermore, evaluation of HER2/neu protein expression based on digital image analysis and not only on conventional eye microscopy improves the accuracy and reliability of immunohistochemical estimation, although that does not demonstrate clinical significance and prognostic value in pancreatic ductal adenocarcinoma.

Aged↗
PubMed2006

Comparison of monopolar electrocoagulation, bipolar electrocoagulation, Ultracision, and Ligasure.

PURPOSE: Hemostasis is a fundamental principle of surgery. We compared the safety and efficacy of monopolar electrocoagulation (ME), bipolar electrocoagulation (BE), Ligasure (LS), a modern bipolar vessel sealing system, and Ultracision (UC), a system of ultrasound energy based shears. We also studied the healing process after their use. METHODS: We used each of the above methods to coagulate and divide the short gastric vessels of 16 white male New Zealand rabbits. The animals were killed after 3, 7, 14, or 21 days, and the coagulation sites and the adjacent gastric wall were examined histologically. RESULTS: LS and UC achieved complete hemostasis without any complications. Conversely, ME and BE often resulted in failed coagulation and perforation of the neighboring gastric wall from a side thermal injury. Histologically, LS demonstrated the mildest side thermal injury and the fastest healing process. We noted greater thermal injury and inflammatory response after UC than after LS on days 7 and 14; however, ME and BE caused the most severe lesions. CONCLUSIONS: LS and UC are clearly the safest and most efficient methods of coagulation, whereas ME and BE could cause serious clinical and histological complications. We found histological evidence that UC causes a slightly greater inflammatory response than LS, and the clinical implications of this warrant further investigation.

Animals↗
PubMed2006

Finasteride effects on hypoxia and angiogenetic markers in benign prostatic hyperplasia.

OBJECTIVES: To assess the effects of finasteride on angiogenetic and hypoxia markers in benign prostatic hyperplasia. METHODS: A total of 178 patients aged 51 to 85 years (mean 68.7) with benign prostatic hyperplasia and awaiting transurethral prostate resection were prospectively randomized into a group of patients receiving finasteride (group 1; 88 patients) and a group of patients who received no medication until transurethral prostate resection (group 2; 90 patients). Tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 for microvessel density (MVD), vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1alpha (HIF-1alpha). RESULTS: Blood loss during transurethral prostate resection was significantly higher in group 2 compared with group 1 (P <0.001). The distribution of CD34 immunostaining was mainly at the suburethral prostate. MVD, VEGF, and HIF-1alpha values were significantly lower statistically (P <0.001) in group 1 compared with group 2. In the finasteride group (group 1), the positive correlation of the immunoreactivity of CD34 and HIF-1alpha, VEGF and HIF-1alpha, and VEGF and CD34 was statistically significant (P <0.001). In the same group, MVD and VEGF and HIF-1alpha expression correlated statistically with the treatment duration. CONCLUSIONS: Finasteride administration in benign prostatic hyperplasia results in statistically significant suppression of MVD, VEGF, and HIF-1alpha in a time-dependent manner.

Aged↗
PubMed2006

Abruptio placentae and idiopathic arterial calcification in a stillborn.

We report a case of idiopathic arterial calcification in a stillborn of 22 weeks gestational age. The pregnancy was complicated by abruptio placentae and the postmortem examination showed widespread arterial calcification in the placenta, as well as in the pulmonary, renal, cerebellar, and brain arteries.

Abruptio Placentae↗
PubMed2006

Maltoma of the thyroid and Sjögren's syndrome in a woman with Hashimoto's thyroiditis.

We report the case of a 70-yr-old woman with maltoma of the thyroid, Sjögren's syndrome, and a history of Hashimoto's thyroiditis. The patient underwent a total thyroidectomy for a recently growing mass of the thyroid, while being treated with L-thyroxine for Hashimoto's thyroiditis. Postoperatively, routine histologic examination was consistent with the diagnosis of chronic lymphocytic thyroiditis of autoimmune etiology. Three years later, the patient presented with high temperature, anorexia, and coughing. This time, a microscopic examination of deeper thyroid tissue sections and an immunohistochemical study revealed a low-grade, non-Hodgkin lymphoma, MALT type. Simultaneously, the diagnosis of Sjögren's syndrome was established and the patient is currently under investigation for generalized lymphoma. This case clearly demonstrates the difficulty in differentially diagnosing Hashimoto's thyroiditis from low-grade MALT lymphoma by the use of routine histologic examination.

Aged↗
PubMed2006

Immunohistochemical investigation of angiogenic factors in parathyroid proliferative lesions.

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult in several cases. Endoglin (CD105) is a proliferation-associated and hypoxia-inducible protein abundantly expressed in angiogenic endothelial cells. Vascular endothelial growth factor (VEGF) induces angiogenesis and VEGF-R2 is a tyrosine kinase receptor expressed early in development by endothelial cell precursors. We attempted to examine whether immunohistochemical expression of CD105, VEGF and VEGF-R2 may be useful in distinguishing between parathyroid hyperplasia and neoplasia as well as to elucidate, to some extent, the mechanism of neovascularization in proliferative lesions of the parathyroid gland. DESIGN: Tissue specimens were taken from 38 patients with primary hyperparathyroidism (HPT) (17 adenomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to endoglin, VEGF and VEGF-R2 were applied to detect angiogenic endothelial cells. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Positive CD105 immunoreaction was significantly increased in parathyroid adenomas by comparison with primary hyperplasias (P = 0.033) and with secondary hyperplasias (P = 0.033). When parathyroid adenomas, primary hyperplasia and secondary hyperplasia specimens were comparatively evaluated, VEGF immunoreaction was much more common in adenomas (P = 0.018). In addition, in samples with secondary hyperplasia, VEGF-R2 immunoreactivity was positively linked with VEGF expression as well as with the apoptotic index of parathyroid cells (P = 0.038 and 0.010 respectively). In secondary hyperplasia specimens, an inverse correlation between cyclin D1 immunoexpression and angiogenic indexes, such as CD105 and VEGF, was noticed (P = 0.007 and 0.0017 respectively). CONCLUSIONS: This study shows increased angiogenesis in parathyroid adenomas compared with parathyroid proliferative lesions. In secondarily hyperplastic glands increased angiogenesis and increased apoptosis occur simultaneously; in the latter glands, the overexpression of cyclin D1 does not appear to be the genetic abnormality responsible for increased angiogenesis.

Adenoma↗
PubMed2005

Cyclin D1 protein tissue detection in laryngeal cancer.

Cyclin D1 (CCND1) is a set of periodic regulatory proteins that is believed to govern cell cycle transit from G1 into S phase. Overexpression of CCND1 leads to abnormal cellular proliferation which underlies processes of tumorigenesis; CCND1 can thus function as a cooperative oncogene in cell transformation. In the present study we investigate the immunohistochemical expression of CCND1 in a well-documented series of 58 laryngeal squamous cell carcinomas (LSCC) and search for statistical associations between CCND1 index and various clinicopathological parameters including several immunomarkers' expression as well as patients' disease-free survival. Tissue sections from archival paraffin blocks were stained using the avidin-biotin-peroxidase complex method; the H-295 rabbit polyclonal antibody was applied at dilution of 1:150. The percentage of CCND1 immunoreactive tumor cells for each tumor was counted by an image analysis system. CCND1 staining was confined to cell nuclei and, in the examined samples, ranged from undetectable (i.e. 0% of tumor cells, n = 6) to the majority of tumor cells (i.e. 89% of tumor cells) with mean value: 15.73%. In tumor adjacent, non invasive lesions, strong CCND1 staining was noticed in areas with cellular atypia. In cases with nodal metastases, no change in CCND1 expression in the nodal metastases compared with the primary tumors was observed. p53 protein accumulation in malignant cells was positively linked with CCND1 index (Mann-Whitney U: 205.5, p = 0.034). CCND1 expression appears to be an early event in processes of tumorigenesis and tumor progression in some LSCC. Apart from p53 protein accumulation, CCND1 immunohistochemical expression does not seem to correlate with nodal metastasis, disease recurrence or any other clinicopathological prognostic indicator.

Adult↗
PubMed2005

Expression of mismatch repair enzymes, hMLH1 and hMSH2 is not associated with microsatellite instability and P53 protein accumulation in basal cell carcinoma.

Microsatellite instability (MSI) constitutes an alternative-to the chromosomal instability-pathway of carcinogenesis for certain tumour types with prognostic and therapeutic significance for the respective patients. MSI is caused by mutations in mismatch repair (MMR) genes, mainly hMLH1, hMSH2, leading to a defective MMR system. The role of MSI in basal cell carcinoma (BCC) has not been clearly delineated yet. p53 gene as a target for ultraviolet radiation-induced mutations may enhance genomic instability in BCC, with loss of its function. Our aim was to investigate the involvement of MSI and expression of hMLH1 and hMSH2 in parallel with P53 protein accumulation in the pathogenesis of BCC and its possible correlation to the clinicopathological features of the patients. The presence of MSI was investigated in 76 BCCs using mononucleotide microsatellite markers, BAT-25, BAT-26 and TGF-beta receptor type II (TGF-beta-RII). Additionally, 3 dinucleotide markers were analysed in 20 cases in which matched normal tissue was available. The expression of hMLH1, hMSH2 and P53 proteins was evaluated by immunohistochemical analysis. Alterations of the BAT-26 marker were observed in one fibroepithelioma of Pincus, one nodular and one multifocal superficial BCC. A keratotic BCC showed an altered BAT-25 locus. Two samples, a multifocal superficial and a nodular BCC, displayed MSI at two markers (BAT-25 and BAT-26; and BAT-25 and TGF-beta-RII, respectively). Three more cases, a metatypical, a multifocal superficial and a signet ring BCC exhibited frameshift mutations in the TGF-beta-RII. No sample showed length alterations at the dinucleotide markers examined. hMLH1 and hMSH2 protein immunohistochemical expression was scored positive in 46 and 49 out of 52 cases respectively. P53 accumulation was observed in 27 out of 56 samples. Correlation of the molecular and immunohistochemical findings with the clinicopathological parameters produced no statistically significant results. No correlation between MSI and hMLH1, hMSH2 or P53 protein expression was determined. MSI appears to play a minor role in the pathogenesis of BCCs being present only in a small subset of such tumours.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Hypoxia, angiogenesis and apoptosis markers in locally advanced rectal cancer.

BACKGROUND AND AIMS: Hypoxia-inducible factor 1alpha (HIF-1alpha) is a critical regulatory protein of cellular response to hypoxia. HIF-1alpha triggers the angiogenic process through activation of the vascular endothelial factor (VEGF) gene. The bcl-2 anti-apoptotic and the death promoting p53 genes, regulate the apoptotic cell death. We investigated the relationship between hypoxia, angiogenesis and apoptosis and their prognostic impact in patients with advanced rectal cancer. PATIENTS AND METHODS: The immunohistochemical expression of HIF-1alpha, VEGF, p53 and bcl-2 and the determination of microvessel density (MVD), apoptotic index (AI) were carried out in tumour tissue samples obtained from 92 patients with locally advanced rectal cancer (LARC) (T3,4/N+/-). RESULTS: HIF-1alpha high reactivity and VEGF overexpression were noted in 47.8 and 44.6% of the examined cases, respectively. They significantly correlated with lymph node metastasis (P<0.001) and low rectal location (P=0.016). HIF-1alpha expression was directly correlated with VEGF up-regulation (P<0.001) and MVD (P<0.001). VEGF expression was closely interrelated with MVD (P<0.001). In univariate analysis advanced grade, infiltrative pattern of tumour growth, vascular invasion, positive lymph node status, HIF-1alpha expression and VEGF upregulation were related to decreased disease-free and overall survival. In multivariate analysis, only high HIF-1alpha reactivity and positive lymph node status emerged as independent variables of adverse prognostic significance. CONCLUSION: HIF-1alpha and VEGF may play an important predictive and prognostic role in patients with LARC.

Aged↗
PubMed2005

Evaluation of hypoxia-inducible factor 1alpha overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma.

OBJECTIVES: To investigate the possible role of hypoxia-inducible factor 1alpha (HIF-1alpha, a transcription factor important in regulating O(2) homeostasis and physiological responses to oxygen deprivation) in the recurrence and progression of superficial urothelial bladder cancer, and to examine its expression in relation to proliferation status, apoptotic activity and intratumoral angiogenesis. PATIENTS AND METHODS: Paraffin wax-embedded tissue from 140 patients with superficial primary urothelial bladder carcinoma was immunostained for HIF-1alpha, Ki-67, single-stranded DNA antibody for apoptotic cells, p53, bcl-2, vascular endothelial growth factor and CD31 antigen. We calculated the proliferative rate, the apoptotic index and the microvessel density (MVD). The mean (sem) follow-up was 46 (3.5) months, within which 86 patients relapsed while 18 progressed to a higher tumour stage and/or grade. RESULTS: HIF-1alpha expression was more common in high-grade superficial urothelial carcinomas. The positivity was related to increased proliferative activity (P = 0.012), apoptotic rate (P = 0.006) and MVD (P < 0.001). HIF-1alpha overexpression had a marginal adverse influence on progression-free survival (P = 0.058; univariate analysis), but when combined with p53 overexpression, the unfavourable impact was statistically important (P = 0.028). In multivariate analysis, only grade and the high Ki-67 labelling index were significant predictors of recurrence-free survival, while T-stage and the HIF-1alpha+/p53+ phenotype emerged as the only independent variables of adverse prognostic significance for time to progression. CONCLUSIONS: HIF-1alpha overexpression combined with aberrant mutant p53 nuclear protein accumulation seem to indicate an aggressive phenotype, suggesting a potential biological model predictive of future risk of disease progression in patients with superficial urothelial bladder carcinoma. These indicators may be helpful in clinical practice to discriminate superficial bladder cancer worth a more intensive follow-up, or more aggressive treatment.

Adult↗
PubMed2004

Tissue detection of natural killer cells in colorectal adenocarcinoma.

BACKGROUND: Natural killer (NK) cells represent a first line of defence against a developing cancer; however, their exact role in colorectal cancer remains undetermined. The aim of the present study was to evaluate the expression of CD16 and CD57 [immunohistochemical markers of natural NK cells] in colorectal adenocarcinoma. METHODS: Presence of NK cells was investigated in 82 colorectal adenocarcinomas. Immunohistochemical analysis was performed, using 2 monoclonal antibodies (anti-Fc Gamma Receptor II, CD16 and an equivalent to Leu-7, specific for CD-57). The number of immunopositive cells (%) was evaluated by image analysis. The cases were characterized according to: patient gender and age, tumor location, size, grade, bowel wall invasion, lymph node metastases and Dukes' stage. RESULTS: NK cells were detected in 79/82 cases at the primary tumor site, 27/33 metastatic lymph nodes and 3/4 hepatic metastases; they were detected in levels similar to those reported in the literature, but their presence was not correlated to the clinical or pathological characteristics of the series, except for a negative association with the patients' age (p = 0.031). CONCLUSIONS: Our data do not support an association of NK cell tissue presence with clinical or pathological variables of colorectal adenocarcinoma, except for a negative association with the patients' age; this might possibly be attributed to decreased adhesion molecule expression in older ages.

Adenocarcinoma↗