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Biomedical subjects

E Sivridis

Publications and source records attributed to E Sivridis.

At least 55 records · Page 3Linked to original sources

Tumor angiogenesis is associated with MUC1 overexpression and loss of prostate-specific antigen expression in prostate cancer.

The biological potential of prostate cancer is highly variable and cannot be satisfactorily predicted by histopathological criteria alone. Therefore, additional and more precise information is desirable. Although angiogenesis has been suggested as being of prognostic importance in many human cancers, and MUC1, also known as episialin, was thought to be responsible for the development of metastasis, the role of these parameters in prostate cancer remains unclear. The aim of this study was to investigate whether angiogenesis, assessed as microvessel density (MVD), was correlated with the expression of prostate tumor MUC1 and prostate-specific antigen (PSA) or with histopathological grade at diagnosis, and to determine whether any of these factors might provide additional information with regard to prostate tumor biology. Paraffin-embedded material from 60 patients with prostate carcinoma was examined immunohistochemically, using the monoclonal antibody CD31 to determine MVD, and the monoclonal antibodies CCE831 and ER-PR8 to assess MUC1 and PSA expression, respectively. The tumors were categorized according to the Gleason grading system. MUC1 overexpression was significantly related to a high intratumoral angiogenesis (P = 0.02). By contrast, a high PSA expression by prostate cancer cells was associated with low MVD (P = 0.03). No correlation was found between MUC1 and PSA expression. Usually, high-grade tumors were not PSA-expressive and tended to display increased angiogenesis. These differences, however, were not of statistical significance. Similarly, there was no statistically significant association between histological grade and MUC1 expression or angiogenesis. It is suggested that PSA may have a direct suppressive effect on new blood vessel formation in prostate cancer, whereas the expression of MUC1 in this tumor may be connected with an angiogenic phenotype. Additional studies are obviously needed to clarify the precise role of these proteins in prostate cancer.

Cytoplasm↗

Appraisal of imprint cytology in the diagnosis of mucinous carcinoma of the breast: a case report.

A case of mucinous carcinoma of the breast is reported in a female aged 71 years. On gross examination of the left mastectomy specimen two relatively well-circumscribed masses with a gelatinous cut surface were found. Touch imprint cytology was consistent with a low-grade malignancy and histologic and histochemical examination revealed a mucinous carcinoma. Careful prospective correlation between the cytological appearances of cells in imprints and the subsequent histopathology may lead to a more precise cytodiagnosis of a tumor associated with a comparative good prognosis.

Adenocarcinoma, Mucinous↗

Primary diffuse large B-cell lymphoma of the breast: a case report.

Mammary non-Hodgkin's lymphomas are uncommon and account for 2% of all extranodal lymphomas. Stringent diagnostic criteria are applied in the diagnosis of primary lymphoma considering that the breast is a recognized site for disseminated extranodal lymphoma. Our case report was established by histology alone.

Aged↗

Abdominal wall endometriosis--ultrasound research: a diagnostic problem.

Abdominal wall endometriosis (AWE) is a rare event. Only a few reports in the literature mention sonographic features of this clinical entity. We describe a case of a young woman with subcutaneous endometriosis under the surgical scar of a previous cesarean section. Physical examination, ultrasound findings, histopathological features and differential diagnostic problems are discussed. Ultrasound examination, in combination with clinical history, is a useful method in the diagnosis of abdominal wall endometriosis and the avoidance of diagnostic pitfalls.

Abdominal Muscles↗

Expression of fibrillar proteins and vimentin in developing chorionic villi is related to fetal maturation.

Using an immunocytochemical technique, the extracellular matrix components fibronectin, vimentin, laminin and collagen type IV were investigated in human chorionic villi of various stages of development. Fibronectin and laminin were consistently positive throughout embryonic development. Vimentin and collagen type IV were negative in first and second trimester chorionic villi, but became positive in term placentas. With the exception of laminin, all extracellular matrix molecules were detected in the villous stroma and, with the exception of vimentin, they were localized in the basement membranes. Our data suggest that fibronectin and laminin are essential components of the villous structure, while the presence of vimentin and collagen type IV in the chorionic villi should be regarded as an indicator of fetal maturation.

Chorionic Villi↗

Imprint cytology of non-specific granulomatous mastitis.

Non-specific granulomatous mastitis (NSGM) is a tumor-like inflammatory condition involving breast lobules. Its recognition is of great significance because of clinical masquerade to invasive carcinoma. A 25-year-old woman developed a palpable breast lump with clinical and mammographic findings suggestive of malignancy. Touch imprint cytology of the excised lump was consistent with a granulomatous inflammation while histopathological examination documented a NSGM with central necrosis. Clinical, radiologic and laboratory testing failed to identify any specific causative agent.

Adult↗

Expression of the intermediate filament vimentin and fibrillar proteins of the extracellular matrix related to embryonal heart development.

During organogenesis, the heart is one the first organs to develop and the earliest organ to function. The early appearance of cardiac activity in the tubular hearts of chick and rat embryos was noted many years ago. It arises from two plates of the splanchnic mesoderm which fuse to form a single tubular structure composed of endocardial and myocardial cells and, between them, the extracellular cardiac matrix. There is considerable variation in the formation of the extracellular matrix in the various regions of the heart during development. The endocardial lining cells of the vertebrate embryos show a regional specificity that remains an unexplained phenomenon in cardiac morphogenesis. The great majority of the endocardial lining cells remain epithlial. However, a restricted population of endothelial cells, lining the atrioventricular (AV) canal and the reputed proximal outflow tract (OT), transforms into mesenchyme; the latter being the reputed progenitor of the valves and membranous septa. The purpose of this study was to investigate the extracellular cardiac matrix of the human fetal heart in different regions and in various stages of development, and also the heterogeneity of the endocardial cell lining, in connection with the endothelial cells of other cardiac vessels. Identification of the mesenchymal cells/extracellular matrix was confirmed by immunohistochemical techniques using the following monoclonal antibodies: actin, desmin, vimentin, collagen IV and fibronectin. The present results provide evidence that the extracellular matrix of the heart is of mesodermal origin but at the level of the valves the mesenchyme is derived from the endothelial lining cells rather than the primitive mesenchyme.

Antibodies, Monoclonal↗

Biomagnetic activity in the female breast at various physiological states.

PURPOSE: To investigate the biomagnetic activity produced physiologically by the various normally occurring states of the female breast: puberty, reproductive age, pregnancy, lactation and menopause. METHOD: The mammary glands of 90 healthy women were examined using a Superconducting Quantum Interference Device (SQUID). RESULTS: Biomagnetic activity was low at puberty (105.46+/-3.77 fT/square root(Hz)) and the menopause (111.66+/-25.06 fT/square root(Hz)), but was high during the reproductive years (142.13+/-20.70 fT/square root(Hz)), particularly in the hyperplastic states of late pregnancy (221.86+/-12.14 fT/square root(Hz)) and lactation (252.73+/-54.77 fT/square root(Hz)). The results were statistically significant (p<0.0001 ANOVA test). CONCLUSION: Our observations indicate the importance of SQUID in understanding the biomagnetic activity of the female breast at the various physiological states of life.

Adolescent↗

Thioredoxin expression is associated with lymph node status and prognosis in early operable non-small cell lung cancer.

PURPOSE: Thioredoxin (TRX), a low molecular weight protein, exerts reduction-oxidation control over a number of transcription factors involved in cell activation and proliferation. High TRX mRNA levels have been found in lung carcinomas, a trait associated with a growth and survival advantage. EXPERIMENTAL DESIGN: In this study, we examined the immunohistochemical expression of human TRX in normal lung and in 102 primary non-small cell lung carcinomas. RESULTS: In normal lung, the staining for TRX was cytoplasmic in the respiratory bronchial epithelium, alveolar epithelium, and alveolar macrophages. Bronchial glandular cells demonstrated a mixed nuclear and cytoplasmic staining. In lung carcinomas, the pattern of expression for TRX was predominantly cytoplasmic and only occasionally nuclear. A strong association between absence of TRX expression and regional lymph node negativity was observed (P = 0.004). High proliferation index, as detected with Ki-67 antibody, was associated with high TRX expression (P = 0.02). A significant correlation between high cytoplasmic p53 reactivity and low TRX expression was observed (P = 0.04). No association with grade, tumor stage, histology, or bcl-2 was noted. A significant coexpression of TRX with human activator protein endonuclease 1 was recorded (P = 0.04). Absence of TRX expression was associated with a better outcome (P < 0.05). CONCLUSIONS: We conclude that overexpression of TRX in non-small cell lung carcinomas is indicative of a more aggressive tumor phenotype and is associated with bad prognostic features and possibly with a poorer outcome.

Aged↗

Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy.

PURPOSE: Carbonic anhydrases are proteins involved in the catalytic hydration of carbon dioxide to carbonic acid. Recent studies show that carbonic anhydrase 9 (CA9) is up-regulated by hypoxia and that its immunohistochemical tissue distribution follows the distribution of the radiosensitizer pimonidazole (C. C. Wykoff et al., Cancer Res. 60: 7075-7083, 2001). Therefore, CA9 expression may show hypoxia levels of clinical importance. EXPERIMENTAL DESIGN: We assessed the expression of CA9 and the microvessel density (MVD; CD31-positive) in 75 locally advanced squamous cell head and neck cancers treated with concurrent chemoradiotherapy with carboplatin. RESULTS: Strong membrane/cytoplasmic CA9 expression, noted in 20/75 (26.6%) tumors, mainly occurred in tumors with very poor vascularization (expression in 63% versus 14%; P < 0.0001), was located around areas of focal necrosis, and was related to poor complete response rate (40% versus 70%; P = 0.02). These observations suggested that CA9 might be a marker of clinically important hypoxia. Combining the CA9 staining and the tumor angiogenicity (MVD), we identified three groups of patients: (a) hypoxic tumors; (b) euoxic highly angiogenic tumors; and (c) euoxic non-highly angiogenic tumors. Groups (a) and (b) had a very poor local relapse-free survival (P < 0.0001). CONCLUSIONS: Stratification of patients undergoing radical radiotherapy using the CA9/MVD model may be useful for the individualization of therapeutic strategies combining antiangiogenesis and hypoxia targeting with radiotherapy.

Antigens, Neoplasm↗

Extragonadal retroperitoneal endodermal sinus tumor in an eight-month-old female infant.

We describe a rare case of an extragonadal retroperitoneal endodermal sinus (yolk sac) tumor in the minor pelvis. Radiologic investigation, which included abdominal ultrasound and computed tomography (CT), showed a large soft tissue mass occupying the pelvic cavity. Radionuclide bone scans demonstrated bone metastases. The serum alpha fetoprotein was elevated. Pathologic examination of the surgical specimen revealed extragonadal yolk sac tumor. Immunohistochemically, the tumor was positive for a-feto-protein and cytokeratins. After postoperative combination therapy, follow-up CT showed decreasing tumoral disease, while serum alpha fetoprotein returned to normal.

Endodermal Sinus Tumor↗

Marginal-zone B-cell lymphoma, extranodal-malt-type: report of three cases.

A high proportion of extranodal lymphoid infiltrates are diffuse small lymphocytic proliferations [1, 2] and therefore pose a particularly challenging diagnostic problem [1-4]. Their benign or malignant nature cannot be determined using clinical and radiologic criteria. The application of traditional morphologic criteria (i.e., cytologic maturity and polymorphism favor benignancy, while cytologic atypia and monomorphism favor malignancy) [5, 6], has probably improved diagnostic accuracy. However, these criteria generally have not been helpful in evaluating the large number of lymphoid infiltrates composed of monomorphic collections of small cytologically-mature appearing lymphoid cells [1-4] and, therefore, have not always accurately predicted clinical behavior. Extranodal lymphoid proliferations are also of considerable biologic interest since their pathogenesis and natural history have not been fully elucidated. Localized non-Hodgkin's lymphoma, extranodal-MALT-type. was diagnosed in our Department in three cases: Two arose in the orbit and the third one in the tonsil. The tumors had a typical histologic appearance. The microscopical features and immunohistochemical profile are discussed.

Aged↗

Cancer vascularization: implications in radiotherapy?

PURPOSE: Although hypoxia is considered a major cause of failure of radiotherapy, the mechanisms of tumor hypoxia are unclear, and effective ways for its correction or targeting are missing. Tumoral vasculature is the vehicle for the hemoglobin to reach the tumoral stroma. Although anemia has long been focused on as an important parameter related to tumor hypoxia, differences in vascular density may also affect the intratumoral access of hemoglobin. METHODS AND MATERIALS: In the present study, we examined the vascular density in 1459 human carcinomas. The distribution of the vascular density within tumors was studied in 436 non-small-cell lung carcinomas and 298 breast carcinomas. RESULTS: The vascular density was found to vary up to 22-fold even among tumors of the same histology. Overall, the vascular density was significantly higher in the tumor periphery as compared to inner areas. Three different patterns of vascularization were identified in both lung and breast cancer specimens; (1) tumors with low or (2) tumors with high vessel density throughout the tissue section, and (3) tumors with high vessel density in the tumor periphery and low in inner areas. The death rate following surgery showed a direct association with the vascular density in lung, breast, colon, and endometrial cancer. In inoperable gastric cancer patients treated with chemotherapy, and in head and neck cancer patients treated with radical chemoradiotherapy there was a 'U-like' association of the death rate with the vascular density suggesting that very low (poor oxygen and drug availability) and very high (intensified angiogenic pathways) vascularization are both linked to poor outcome. CONCLUSION: The present study stresses the importance of the vascular density as a putative variable that may have affected the results of large clinical trials that investigated the role of anemia, hyperbaric oxygen, hypoxic sensitizers, or even of combined chemoradiotherapy in the outcome of radiation treatment.

Adenocarcinoma↗

Vascular endothelial growth factor/KDR activated microvessel density versus CD31 standard microvessel density in non-small cell lung cancer.

Vascular endothelial growth factor (VEGF) is an important angiogenic factor, linked to poor outcome in human malignancies including non-small cell lung carcinoma (NSCLC). We used the 11B5 monoclonal antibody recognizing the VEGF/KDR complex (R. A. Brekken et al., Cancer Res., 58: 1952-1959, 1998) to assess the VEGF expression in cancer cells and the VEGF/KDR activated microvessel density (aMVD) in early operable NSCLC. The JC70 anti-CD31 monoclonal antibody was used to assess the standard MVD (sMVD). The aMVD was significantly higher in the invading front of the tumors and in the normal lung adjacent to the tumors as compared with normal lung distant to the tumor or to inner tumor areas (P < 0.0002). The sMVD was higher in the normal lung and decreased from the invading front to inner tumor areas (P < 0.0001). However, the vascular activation (aMVD:sMVD) was 4-6 times higher in the tumor areas as compared with lung from normal individuals (36-58% versus 9%; P < 0.0001). Fibroblast 11B5 reactivity, noted in 25% of cases, correlated with high aMVD and sMVD in the inner tumor areas. Multivariate analysis showed that aMVD was the most potent and independent prognostic factor (P = 0.001; t-ratio, 3.28). It is concluded that intense VEGF/KDR angiogenic pathway activation is a tumor-specific feature in more than 50% of NSCLC cases and is associated with poor postoperative outcome. Clinical trials involving targeting of the VEGF/KDR-positive vasculature with specific antibodies, such as 11B5, are, therefore, encouraged.

Adenocarcinoma↗

'Invading edge vs. inner' (edvin) patterns of vascularization: an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer.

Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and migration stimuli produced by cancer or tumour stromal cells. Although this active angiogenesis takes place in the tumour periphery, the process of vessel growth and survival in inner areas and its clinical role remain largely unexplored. The present study compared the microvessel score (MS) as well as the single endothelial cell score (ECS) in the invading edge and in inner areas of non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was observed in both peripheral and inner tumour areas; the edvin type 2, where a high MS was noted in the invading front but a low MS in inner areas; and the edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS was high in the invading edge in edvin type 2 and 3 cases and was sharply decreased in both types in inner areas, suggesting that endothelial cell migration is unlikely to contribute to the angiogenic process in areas away from the tumour front. Expression of the vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) was associated with a high MS in the invading edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP expression was associated with edvin type 2, showing that VEGF (and not TP) contributes to the preservation of the inner vasculature. Both edvin type 2 and 3 cases showed an increased incidence of node metastasis, but edvin type 3 cases had a poorer prognosis, even in the N1-stage group. The present study suggests that tumour factors regulating angiogenesis and vascular survival are not identical. A possible method is reported to quantify these two parameters by comparing the MS in the invading edge and inner areas (edvin types). This observation may contribute to the evaluation of the effectiveness of different therapeutic approaches, namely vascular targeting vs. anti-angiogenesis.

Carcinoma, Non-Small-Cell Lung↗

Lectin-binding patterns in normal, hyperplastic and neoplastic endometrium: the prognostic value of concanavalin A.

Lectins are proteins and glycoproteins of non-immune origin which bind specifically to carbohydrate residues, agglutinate cells and/or precipitate complex carbohydrates. Lectin-binding patterns in normal, hyperplastic and neoplastic endometria were studied using four biotinylated lectins (Con A, LCA, e-PHA, l-PHA) and the avidin-biotin-peroxidase technique. Canavalia ensiformis agglutinin (ConA) and Lens culinaris agglutinin (LCA) reacted strongly with the luminal borders and the cytoplasm of epithelial cells but, whilst in normal and benign endometrial tissues the cytoplasmic staining was confined to the apical and the basal aspect of the cells, in endometrial carcinomas and in some atypical hyperplasias lectin binding also occurred in the lateral cytoplasm (Con-A-lat), although in differing proportions of cells. Interestingly, extensive Con-A-lat in the tumour cells was much more frequent in non-endometrioid carcinomas (P<0.05) and was significantly associated with poor histological differentiation (P<0.0001), low oestrogen and progesterone receptor content (P<0.01 and P=0.0001, respectively) and an unfavourable long-term survival (P<0.05). With Phaseolus vulgaris erythroagglutinin (e-PHA) and leucoagglutinin (l-PHA) a linear, rather inconsistent, staining at the level of the basement membranes was observed in the glands: this, also noted with LCA, appeared intact in normal and hyperplastic glands without cytological atypia, and fragmented or absent in malignant glandular structures and in most hyperplastic glands showing cytological atypia. It is concluded that changes in the distribution of lectin-binding molecules in the endometrial cells are associated with the malignant state, whilst the extent of Con-A-lat reflects the biological behaviour of the tumours.

Carcinoma, Endometrioid↗