Biomedical subjects
Publications and source records attributed to Vassiliki Zolota.
Rhabdomyomas are benign tumors in which at least some cells are differentiated as skeletal muscle cells with cytoplasmic cross-striations. Extracardiac adult rhabdomyoma is an extremely uncommon benign neoplasm that usually involves the head and neck region. Rare cases have been reported to involve other sites of the body including mediastinum. We report the fourth case of mediastinal adult rhabdomyoma.
We present a new case of leiomyosarcoma, a very rare clinical entity, arising from the renal pelvis. The primary diagnosis, based on asymptomatic gross hematuria and imaging findings, was tumor of the left kidney. After a left radical nephro-ureterectomy, histology confirmed a leiomyosarcoma of the renal pelvis. No adjuvant treatment was provided and the patient remains healthy 3 years after surgery.
BACKGROUND: This study investigates the correlation of hepatic progenitor cells (HPC) expression with treatment response in patients with chronic hepatitis C. DESIGN: The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All patients were PCR-HCV (+) and received antiviral therapy with interferon or pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group C). Ten normal liver biopsies were used as controls. Liver paraffin sections were subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19) and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34 antigen (b) to in situ hybridization for AFP mRNA and (c) to immunohistochemistry+in situ hybridization. Results were expressed as % of positive cells following morphometric analysis. RESULTS: HPC expression was present in all 87 specimens. In the control biopsies, rare HPC were detected. In the CH cases and according to AFP mRNA expression, the grade for % HPC expression was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01), and transaminase values (P<0.05). CONCLUSIONS: This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.
PURPOSE: This study investigates the expression of tumor growth factors TGFbeta1, TGFbeta2 and TGFbeta3 in tissue material from patients with colorectal carcinoma and evaluates their correlation with known prognostic markers and patient survival. PATIENTS AND METHODS: The study included 124 patients with colorectal carcinoma. According to the TNM classification of malignant tumors, 26 tumors were identified as being stage I, 30 stage II, 48 stage III, and 20 stage IV, whereas 106 tumors were low-grade and 18 high-grade malignancies. On paraffin sections, the streptavidin-biotin technique using antibodies against TGFbeta1, TGFbeta2 and TGFbeta3 was applied. Morphological and immunohistochemical results were correlated with clinicopathologic parameters. RESULTS: TGFbeta1 protein was expressed in 88 out of 124 (71%) carcinomas, whereas TGFbeta2 and TGFbeta3 proteins were detected in all tumors examined. Normal colonic mucosal epithelial cells expressed TGFbeta2 (significantly less as compared to neoplastic cells; p < 0.01) and TGFbeta3 (p > 0.05 compared to neoplastic cells), but not TGFbeta1. Statistical analysis revealed a higher expression of TGFbeta1 in low-grade carcinomas (p = 0.009) and a higher presence of TGFbeta2 in advanced tumors (p = 0.008). TGFbeta1 expression was related with increased disease-free and overall survival (p < 0.05 each). The presence of TGFbeta2 was correlated with worse prognosis (p < 0.05). Cox analysis revealed that besides tumor grade and stage, TGFbeta1 expression constituted an independent prognostic factor. CONCLUSION: This study shows that in adenocarcinomas of the colon, there is a differential expression of TGFbeta1, TGFbeta2 and TGF3. TGFbeta1 may be implicated in the pathogenesis of these tumors, since it is expressed only in neoplastic but not in normal cells. TGFbeta1 is related with an increased disease-free and overall survival and constitutes an independent prognostic factor. In advanced stages, TGFbeta2 seems to be involved in tumor progression and is related with worse prognosis.
Bcl-2 oncoprotein regulates programmed cell death by providing a survival advantage to rapidly proliferating cells, and bax protein promotes apoptosis by enchanting cell susceptibility to apoptotic stimuli. In this study, we assessed the expression of bcl-2 and bax in liver biopsies from patients with chronic hepatitis (CH) Type B (HBV) and C (HCV). The study comprised 65 liver biopsies from 65 patients with HBV (n = 37) and HCV (n = 28) and 10 normal liver biopsies as controls. The HAI score ranged from 3/18-13/18, and the fibrosis Stage, from 1-6 (7 HBV/10 HCV). Pathologic examination included the following: (1) immunohistochemical stains in paraffin sections for bcl-2 and bax protein expression, (2) Western blot analysis (bcl-2 and bax protein levels evaluation), (3) ISH (detection of bcl-2 and bax mRNA), and (4) ISH (TUNEL-ABI [apoptotic body index]). In CH cases, both bcl-2 and bax protein and mRNA were detected in portal and intralobular lymphocytes and in cholangiolar epithelial cells in interface areas and fibrous bands. Bax protein and mRNA was expressed within hepatocytes and epithelial cells of interlobular ducts in portal tracts. Bcl-2 mRNA was present in periportal hepatocytes only in cases with Stage 5-6 fibrosis. Western blot analysis showed a decreased bcl-2 and an increased bax expression toward advanced fibrotic stages. In CH cases, ABI was reverse correlated with the percentage of bcl-2 expression and was correlated directly with the percentage of bax expression (P <.001). The results of this study suggest that in cases of chronic HBV or HCV infection, bax may be involved in the hepatocyte cycle regulation during infection, whereas its expression in intraportal bile duct epithelium implies that this protein enhances susceptibility of these particular cells to apoptosis. The increased bax expression and ABI in fibrosis Stages 1-5, imply that they are responsible for hepatocytes depletion through apoptosis, during progress of liver fibrosis and fibrous tissue accumulation, until cirrhosis is established. Bcl-2 mRNA expression in periportal hepatocytes only in Stages 5 and 6 suggests that this oncogene is involved in the late stages of progressive liver fibrosis and failure and furthermore that periportal hepatocytes are resistant to apoptosis. Bcl-2 expression, in cholangioles of interface area, suggests that this oncoprotein may be involved in growth regulation of these epithelial cells. Further research is warranted to specify the exact role of apoptosis and apoptotic genes involved in liver fibrosis process in cases of chronic HBV and HCV infection. This may lead to new strategies in the management of human liver disease to prevent the progression to chronic liver failure.
Dendritic cells (DCs) are antigen-presenting cells and mature from precursor CD34+ stromal cells (dendritic interstitial cells [DICs]) or monocytes. The aim of the present study was to gain insight into the local immune response to various thyroid lesions. We investigated, immunohistochemically, the presence of S-100+ DCs and CD34+ DICs in 13 papillary carcinomas, 10 follicular carcinomas, 7 follicular adenomas, 1 Hurthle cell carcinoma, 1 Hurthle cell adenoma, 2 medullary carcinomas, 6 undifferentiated carcinomas, and 3 nodular goiters. Dense infiltrates of S-100+ DCs were noted in the majority of papillary carcinomas (mean: 66.4), while moderate infiltrates were observed in follicular adenomas (mean: 23.3), follicular carcinomas (mean: 23.5), and undifferentiated carcinomas (mean: 31.6). The remaining lesions showed slight infiltrates of scattered DCs. DICs were noted exclusively in neoplastic lesions, specifically at the periphery and within the tumor capsule. The increased number of DCs in papillary carcinomas is possibly correlated with their good prognosis. The specific distribution of DICs suggests a possible contribution to growth regulation of thyroid neoplasms.
BACKGROUND: Transforming growth factors-beta (TGF-betas) are multifunctional polypeptides with crucial role as regulators of cellular growth and differentiation. It has been reported that TGF-beta1 plays a biphasic action on tumorigenesis thus inducing or inhibiting malignant properties of the epithelial cells. METHODS: TGF-beta1 expression was analyzed in 56 patients with gastric carcinoma by immunohistochemical methods and compared with the expression of p21, p53, and Ki67, as well as with angiogenesis. The correlation of these markers with clinicopathological parameters was also evaluated. RESULTS: TGF-beta1 expression was detected in 71% of tumors and was more frequent in adenocarcinomas of the intestinal type (p < 0.001). Positivity of p21WAF1, and p53 was observed in 32% and 51% of the tumors, respectively. A high Ki67 proliferating index was detected in 53.5% of the tumors. TGF-beta1 expression was significantly correlated with p21 expression (p < 0.001) and was inversely correlated with microvessel density. p21 expression was also higher in tumors with low proliferating index (p < 0.01). There was no apparent correlation between the expression of these markers and tumor stage, depth of invasion, or lymphnode metastases. CONCLUSION: The findings show that TGF-beta1 may be involved in the activation of the cdk inhibitor p21WAF1 in gastric adenocarcinomas, suggesting p53-independent induction of p21 in gastric cells. TGF-beta1 does not seem to contribute to the alteration of the angiogenic status of these tumors.
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CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix interactions. Recent evidence indicates a role of CD44 in tumor growth and metastatic potential of tumor cells. Moreover, it is widely known that the p53 tumor suppressor gene controls cell proliferation and loss of its normal function may lead to carcinogenesis. To investigate the role of these biomarkers in renal cancer, we analyzed the immunohistochemical distribution of CD44's expression on formalin fixed paraffin embedded tissue from 67 renal cell carcinomas and correlated with clinicopathologic parameters as well as with p53 suppressor gene expression. The monoclonal antibodies CD44 and p53 were applied to the tissues using the streptavidin biotin peroxidase method after microwave antigen retrieval. For CD44 and p53 more than 10% membranous and 5% nuclear staining, respectively, were estimated as positive. CD44's membranous immunoreactivity was detected in 24/67 tumors (35%) and mostly in carcinomas of clear/granular cell type. Nine tumors expressed nuclear immunoexpression of p53 protein (13.4%). Statistically significant correlation was noted between CD44 expression and nuclear grade (P < 0.001), tumor stage (P < 0.001), vascular invasion (P < 0.05) and p53 expression (P < 0.01). These results suggest that CD44s and p53 are markers of tumor progression in renal cell cancer.
The expressions ofp27Kip1 (p27) and p21waf1 (p21) cyclin-dependent kinase inhibitors and p53 were examined in a series of 170 node-negative breast carcinomas (NNBCs) to evaluate their prognostic significance. Low nuclear (p27TN) and cytoplasmic (p27TC) p27 expressions were noted in 66% and 81% of NNBCs, respectively. p21 and p53 overexpressions were detected in 56% and 26%, respectively. Low p27TN was significantly associated with high grade (p=0.001), age < or = 50 years (p=0.01), negative hormone receptors (p<0.001), low p27TC (p<0.001) and p53 overexpression (p=0.02). Low p27TC was associated with negative hormone receptors (p<0.001). p53 overexpression was associated with high grade (p<0.001) and negative hormone receptors (p<0.001). p21 overexpression, although not correlated with the examined parameters, was associated with increased disease-free survival in univariate analysis. In multivariate analysis, p27TN, p27TC, p21 and p53 were not associated with disease-free survival or overall survival. These findings argue against the prognostic value of p27, p21 and p53 in NNBC.