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Biomedical subjects

E Patsouris

Publications and source records attributed to E Patsouris.

At least 55 records · Page 3Linked to original sources
PubMed2001

Increased incidence of sporadic Creutzfeldt-Jakob disease on the island of Crete associated with a high rate of PRNP 129-methionine homozygosity in the local population.

Since the spring of 1997, when the Neurology Department of the University Hospital of Crete admitted its first patient, nine cases (eight neuropathologically confirmed and one probable) of sporadic Creutzfeldt-Jakob disease (sCJD) have been recorded. This represents an annual incidence five-fold higher than expected based on the island's population (0.54 million). Molecular analysis of the prion-protein gene (PRNP) showed no mutations in any of the seven CJD cases studied. Five patients (ages 64-88 years) were homozygous for methionine-129 of PRNP and showed the classic sCJD triad (subacute dementia, myoclonus, periodic electroencephalogram). Brains contained type 1 (unglycosylated 21.5 kDa band) protease-resistant prion protein (PrPres). Two patients (ages 56 and 57 years), both homozygous for valine-129, showed cerebellar ataxia and later dementia not associated with periodic electroencephalogram; brain PrPres was type 2. Genotyping of 205 Cretan controls showed that methionine-129 homozygosity, a susceptibility factor for sCJD, was significantly higher in this population than in other Caucasian populations (57.0% n = 205 vs. 41.5% n = 859, p < 0.0001). These data are the first to relate a high regional incidence rate for sCJD to the distribution of PRNP 129 genotypes in the local population; however, additional factors may be operational.

Age Factors↗
PubMed2000

Apoptosis in bladder carcinomas detected with monoclonal antibody to single-stranded DNA: relation to cell cycle regulators and survival.

OBJECTIVES: To investigate the incidence of baseline apoptosis in relation to p27(Kip1), p53, and p21(Cip1) expression, proliferation status, standard clinicopathologic parameters, and patient outcome. Cell cycle regulators and apoptotic cell death have been implicated in tumor aggressiveness in many human malignancies. Their interaction, however, in the prognosis of patients with transitional cell carcinoma (TCC) of the urinary bladder has not yet received intense scrutiny. METHODS: Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing single-stranded DNA regions in apoptotic nuclei in 103 paraffin-embedded primary TCC specimens. Proliferative activity was expressed as the percentage of Ki-67 positive cells (Ki-67 index). Tissue specimens were also stained for p27(Kip1), p53, and p21(Cip1) proteins. Patients were followed up until death (n = 30) or for an average of 40 months (median 36). RESULTS: The apoptotic index increased with grade, T stage, nonpapillary status, proliferative activity, and p53 expression and was inversely related to p27(Kip1) and independently to p21(Cip1) expression. A negative correlation was found between p27(Kip1) expression and proliferation. The increased apoptotic index had an adverse impact on overall and disease-free survival (univariate analysis) and, along with T stage, was an independent predictor in muscle-invasive TCC. CONCLUSIONS: An increased apoptotic rate, increased proliferative activity, and decreased p21(Cip1) expression are independently interrelated in TCC. More importantly, the assessment of apoptotic potential appears to be more informative than standard prognosticators in predicting overall survival in patients with muscle-invasive TCC.

Adult↗
PubMed1998

Expression of apoptotic and proliferation markers in meningiomas.

Fifty-two intracranial, totally excised meningiomas were immunohistochemically analysed for the expression of bcl-2 and p53 proteins, in parallel with the assessment of the proliferating cell nuclear antigen labelling index (PCNA LI) and the mitotic index (MI). bcl-2 was expressed in 26.8 per cent and p53 in 32.6 per cent of the tumours, exhibiting a similar staining pattern, with low levels of immunoreactive cells. The bcl-2-positive/p53-negative subgroup showed a significant association with a benign histological pattern. Expression of bcl-2 appeared to have no influence on the rate of recurrence; p53 expression was the only factor with prognostic significance for recurrence (p = 0.10). There was no interaction between bcl-2 and p53 expression. The PCNA LI was correlated with the MI and the grade of malignancy, proving to be a useful proliferation marker and an additional indicator of the more anaplastic histological patterns in meningiomas. Proliferation indices appeared to have no correlation with the recurrence rate of totally resected tumours. Meningiomas expressing the bcl-2 protein presented a high proportion of proliferating cells in S phase. In contrast, all the tumours which recurred had a minimal S-fraction of proliferating nuclei. These findings may improve our understanding of the interaction between cell proliferation, expression of apoptotic markers, and recurrence in meningiomas.

Adult↗
PubMed1998

Increased proliferative activity due to necroses induced by pre-operative embolization in benign meningiomas.

The proliferative behaviour of 35 benign intracranial meningiomas was investigated which were embolized for devascularization 3 to 268 hours prior to surgical exstirpation. The nuclear proliferation antigen Ki-67 was visualized by means of the monoclonal antibody MIB1 on formalin fixed and paraffin embedded tissue. Tumor cells and inflammatory reactions were recognized by means of conventional staining procedures and by immunohistochemical detection of HAM56, LCA, HLA-DR, CD15-epitope and vimentin. Extravasation and proliferation of granulocytes, macrophages, lymphocytes and the degree of expression of MHCII antigens was estimated according to a 7-point ordinal scale. Confirming preliminary observations of others the proliferation index within the perinecrotic tumor rim (PIperinec) exceeded that of intact tissue highly significantly. PIperinec peaked at the third to fourth day after embolization and kept this level until the seventh day. The time course of PIperinec was paralleled by that of macrophages, whereas--expectedly--granulocytes occured earlier and lymphocytes and HLA-DR-positivity somewhat later. The timely relationships suggested that the perinecrotic increase in tumor cell proliferation was mainly due to macrophage-born mitogens. Perinecrotic proliferative activity in embolized meningiomas does not reflect genuine tumor proliferation and should not be used for assessment of the presence or degree of malignancy in a given tumor.

Adult↗
PubMed1998

Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression.

AIMS: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas (NHL). METHODS AND RESULTS: Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death (n = 33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response. CONCLUSIONS: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.

Adolescent↗
PubMed1998

Prognostic implications of proliferating cell nuclear antigen (PCNA), AgNORs and P53 in non-Hodgkin's lymphomas.

We investigated the prognostic value of proliferating cell nuclear antigen (PCNA) and p53 oncoprotein expression and of nucleolar organiser region (NOR) scoring, in relation to classic clinicopathological parameters, in a series of non-Hodgkin's lymphomas (NHL). Paraffin embedded tissue from 91 patients with NHL was stained immunohistochemically with the monoclonal antibodies PC-10 (PCNA) and DO-1 (p53) and histochemically with the AgNOR technique. The median follow-up was 48 (4 to 193) months. The impact of PCNA and p53 expression and of AgNOR number on survival was tested using univariate as well as multivariate analysis, in order to circumvent the heterogeneity in histologic grade, type and therapy. Univariate analysis identified seven variables related to overall survival: histologic type and grade, clinical stage, chemotherapy, p53 labelling index (LI), PCNA LI and AgNOR score, whereas only one parameter i.e. histologic grade influenced disease-free survival. In multivariate analysis stage, PCNA LI and AgNOR score predicted independently overall survival. PCNA was also the only independent predictor of post-relapse survival and histologic grade the most important indicator of disease-free survival. In conclusion, PCNA expression and AgNOR number may be better predictors of overall and post-relapse survival than histologic grade. The latter remains the most valuable prognostic indicator of disease-free survival.

Adolescent↗
PubMed1997

Computerized determination of proliferating cell nuclear antigen expression in meningiomas. A comparison with non-automated method.

Proliferating cell nuclear antigen (PCNA) expression has been proven to be a significant marker of cell proliferation in meningiomas, which correlates with growth rate and, as shown by several authors, possibly provides prognostic information concerning biologic behavior. However, the current method for determining PCNA labeling index (LI) is tedious and time consuming like all the nonautomated methods for evaluating cell kinetics, presenting high interobserver and interlaboratory variability and low reproducibility. In the present study, we introduce a semi-automated computer-assisted image analysis method for determining PCNA LI in 38 meningiomas, in parallel with the current nonautomated method. Image analysis technique permits unbiased cell counting, standardizes the degree of staining intensity and provides instant results. By calculating coefficient of variability, the method proved to be highly reproducible. The correlation between the results provided by the nonautomated and the semiautomated image analysis method showed a high agreement between them, with a correlation coefficient, r, of 0.82. In conclusion, we consider that image analysis contributes to the accuracy, reproducibility, and practicality of PCNA LI determination so that along with other useful parameters this significant marker may serve to predict the clinical behavior in meningiomas.

Histological Techniques↗
PubMed1997

Subacute necrotizing encephalomyelopathy (Leigh's disease): a clinicopathologic study of ten cases.

Archival material and clinical data of 10 autopsy cases of Leigh's disease (LS), aged from 44 days to 9 years at death, were reviewed. Development delay, irregular respiration, feeding difficulty, and abnormal eye signs were the most common symptoms. Seizures (five of ten cases) were also frequent. In most patients, the diagnosis of LS was established postmortemly by the presence of symmetrical spongiform lesions affecting several brain centers at autopsy. The histologic examination disclosed associated hypertrophic cardiomyopathy in six cases, while fatty infiltration of the hepatocytes was observed in four cases. Microvesicular degeneration of the renal tubular epithelial cells was also seen in four cases. Our observations suggest that liver and kidney involvement is a component of LS and that this rare entity has to be considered as a polysystematic disorder, able to affect other organs besides the nervous system and the heart, a fact which has not been emphasized enough in the existing literature.

Autopsy↗
PubMed1996

Cystadenolymphoma of the parotid gland an immunohistochemical study of the epithelial component of twenty cases.

Carcinoembryonic antigen, epithelial membrane antigen, Keratin, Desmin, Vimentin, CD30, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 protein, somatostatin and glucagon were looked for using immunohistochemical methods in the epithelial component of 20 parotid gland cystadenolymphomas and 20 normal parotid glands. Carcino-embryonic antigen, ephithelial membrane antigen, S-100 protein, and somatostatin were found in the epithelial cells of most of the cystadenolymphomas. In normal parotid tissue, carcinoembryonic antigen, epithelial membrane antigen, Keratin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and S-100 protein were found in all three types of ductal cells, somatostatin only in intercalated and striated ductal cells, and lysozyme only in acinar and intercalated ductal cells. Desmin and CD30 were found in the epithelial component of seven of the 20 tumors versus none of the 20 normal parotid glands. Glucagon and Vimentin were negative both in tumor epithelial cells and in normal parotid ductal cells. Our results support the theory that cystadenolymphomas arise from epithelial cells. The presence of lysozyme in the epithelial tumor cells and in the intercalated ductal cells of normal parotid tissue suggest that cystadenolymphomas may arise from the intercalated ducts. The presence of S-100 and somatostatin may indicate that the tumor derives from neuroendocrine structures, but further studies are needed to clarify this point.

Adenolymphoma↗
PubMed1995

Pure red cell aplasia associated with true thymic hyperplasia.

Pure red cell aplasia was diagnosed in a 35-year-old otherwise healthy woman. Chest computed tomography (CT)-imaging investigation, detected an upper mediastinal mass corresponding to the thymus gland. A thoracotomy was performed and an enlarged thymus mass was removed, rapidly followed by a full hematologic recovery. Thymic histology confirmed a significant degree of hyperplasia. We conclude that not only thymomas but also other types of thymic pathology may be associated with this type of hematologic dyscrasia.

Adult↗
PubMed1994

Mycobacterial cervical lymphadenitis. A clinicopathological study of 3 cases.

Three adult patients with tuberculous cervical (submandibular) lymphadenitis were treated in the past year in the Department of Oral and Maxillofacial Surgery, Evangelismos Hospital, University of Athens. None had a history of exposure to tuberculosis. In all, the chest X-rays were clear but the PPD tests were positive. All patients underwent excisional biopsy of grossly involved lymph nodes and histological examination and special stains confirmed the diagnosis. The patients were subsequently treated with triple drug administration. Antituberculosis chemotherapy consisted of isoniazid, rifampin and ethambutol and all are well after a follow-up of 9, 10 and 11 months respectively. Medical approaches often failed to diagnose tuberculous cervical lymphadenitis conclusively, and this disease remains a diagnostic and therapeutic challenge, because it mimics other pathological processes. The treatment of choice seems to be surgical excision and long term antituberculosis chemotherapy. Surgery provides a rapid tissue diagnosis, because the histological examination of the excisional biopsy is the most reliable diagnostic test.

Aged↗
PubMed1994

B-cell lymphoma of large multilobated type: an immunohistochemical study of 8 cases and review of the literature.

Large multilobated cell lymphomas represent an heterogenous group comprising both B-cell and T-cell subtypes. The correct lineage identification of each subtype cannot be based on morphologic grounds, as it has already been stressed by other authors, and demands the use of immunophenotyping methods. In this study we review the literature and present eight new cases of large multilobated B-cell lymphoma which have been immunophenotyped in paraffin sections with a panel of monoclonal [L26 (CD20), 4KB5 (CD45R), UCHL1 (CD45RO), MT1 (CD43)] and polyclonal (anti-CD3, anti-kappa, anti-lambda) antibodies. We further investigated the expression of c-myc p62 oncoprotein and of proliferating cell nuclear antigen (PCNA) using the monoclonal antibodies c-myc 1-9E10 and PC-10 respectively. In all cases the neoplastic cells were positive for L26 (CD20) and negative for anti-CD3. Five cases were positive for 4KB5 (CD45R) while six cases stained positively for UCHL1 (CD45RO) or MT1 (CD43). Four cases were monoclonal in respect to light chain restriction. Immunoreactivity with c-myc 1-9E10 and PC-10 was observed in all cases. As far as c-myc 1-9E10 is concerned, positive cells constituted more than 45% of the neoplastic population in six cases, whereas in all cases the percentage of PC-10 positive cells was greater than 45%. The staining pattern was nuclear and/or cytoplasmic for c-myc 1-9E10 but solely nuclear for PC-10. The elevated c-myc and PCNA expression are indices of high proliferation rate in this type of lymphoma and may suggest a high malignancy grade.

Adolescent↗
PubMed1993

A comparative assessment of proliferating cell nuclear antigen, c-myc p62, and nucleolar organizer region staining in non-Hodgkin's lymphomas: a histochemical and immunohistochemical study of 200 cases.

Proliferating cell nuclear antigen (PCNA) and c-myc p62 oncoprotein are two nuclear proteins expressed in proliferating and transformed cells. They can be recognized immunohistochemically in paraffin sections by the monoclonal antibodies PC-10 and c-myc 1-9E10, respectively. On the other hand, nucleolar organizer regions (NORs) are loops of DNA that carry the r-RNA genes and can be visualized in paraffin sections as black dots (AgNORs) using a silver impregnation method. It has been suggested that the mean number of AgNORs may reflect the cellular kinetics of a tumor. We independently examined 200 cases of non-Hodgkin's lymphomas using the monoclonal antibodies PC-10 and c-myc 1-9E10, as well as the AgNOR method. Our study shows a very significant correlation between PCNA, c-myc expression, and AgNOR count on the one hand and histologic grade on the other (P < .001), although a significant overlap among the three grades exists. PC-10, c-myc 1-9E10, and AgNOR scores are all shown to be linearly related, even though significant discrepancies were observed, and the correlation is stronger between PCNA and AgNORs (PCNA v c-myc p62, r = .551; PCNA v AgNORs, r = .746; c-myc p62 v AgNORs, r = .529; P < .001). A remarkable finding is that the intermediate group of lymphomas is heterogeneous as far as the proliferative rate is concerned: diffuse large cell cleaved/non-cleaved lymphomas (category G of the Working Formulation) are characterized by a significantly higher proliferative index, as evidenced by the elevated PCNA, c-myc p62, and AgNOR scores, in comparison with the other types of intermediate-grade lymphomas (P < .001). However, the proliferative rate is lower than that of the high-grade lymphomas (PCNA, P < .05; c-myc p62, P < .001; AgNORs, P < .005). No significant difference exists between B-cell and T-cell lymphomas except for the higher expression of c-myc p62 in intermediate-grade B-cell lymphomas, obviously due to the higher proliferative rate of diffuse large cell lymphomas. Based on our findings, it appears that the combination of PCNA, c-myc p62, and AgNORs provides an accurate estimate of the proliferative rate of non-Hodgkin's lymphomas in paraffin sections. Clinical studies may show whether this information has prognostic value independent of histologic classification. In addition, our results suggest that category G (diffuse large cell) lymphomas may belong to a malignancy grade higher than the intermediate grade, a suggestion consistent with their more aggressive biologic behavior.

Antigens, Neoplasm↗
PubMed1993

Lymphoepithelioid cell lymphoma (Lennert's lymphoma): clinical features derived from analysis of 108 cases.

In a retrospective analysis of 108 patients with lymphoepithelioid cell lymphoma (LeL) (median age 60, range 21-87 years) initial extent of disease was Ann Arbor stage I in 9%, II in 19%, III in 35%, and IV in 37% of the patients with a high incidence of generalized lymphadenopathy (71%) but seldom extralymphatic disease (13%). Unstable spontaneous remissions were observed occasionally. Complete response rates were 75% in the patients treated with radio- and/or chemotherapy but relapse occurred in 65%. Median overall survival was 16 months with a significantly better prognosis for stage I/II than for stage III/IV disease (P = 0.014). LeL thus seems to possess an unfavourable prognosis possibly to be improved by standardized treatment approaches.

Adult↗
PubMed1990

Lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells. Histologic and immunohistochemical findings.

Fifty-four lymph node biopsy specimens from 36 patients with lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells (LPICep) were studied by light microscopy using conventional histologic and immunohistochemical techniques. Three other patients with extranodal involvement only were also included in the study. Of a total of 39 patients, 31 had the polymorphic subtype, six the lymphoplasmacytoid subtype, and two the lymphoplasmacytic subtype. Cellular composition and histologic structure are described in detail as a basis for discriminating LPICep from similar lymphomas with a high content of epithelioid cells, especially from lymphoepithelioid cell lymphoma (Lennert's lymphoma), angioimmunoblastic peripheral T-cell lymphoma with a high content of epithelioid cells, and Hodgkin's disease, mixed cellularity type with a high content of epithelioid cells. In 10 patients (26%) LPICep developed into a high-grade malignant lymphoma of B-immunoblastic type. Forty-seven biopsy specimens were studied with the peroxidase-antiperoxidase method to detect intracytoplasmic immunoglobulin. Plasma cells and plasma cell precursors revealed a monotypic immunoglobulin pattern in all specimens. In 25 biopsy specimens in which giant cells resembling Sternberg-Reed and Hodgkin's cells were found, these cells were CD15 negative. A comparison of the main clinical and laboratory data in these four lymphomas with a high content of epithelioid cells revealed both similarities and differences.

B-Lymphocytes↗
PubMed1989

Angioimmunoblastic lymphadenopathy--type of T-cell lymphoma with a high content of epithelioid cells. Histopathology and comparison with lymphoepithelioid cell lymphoma.

A peripheral T-cell lymphoma with a high content of epithelioid cells--an entity that reveals morphologic and clinical characteristics resembling those seen in angioimmunoblastic lymphadenopathy (AILD)--was separated from lymphoepithelioid cell lymphoma (Lennert's lymphoma, or LeL); it was considered a variant of the AILD type of peripheral T-cell lymphoma (AILD-PTCLep). A histologic evaluation of 135 lymph node biopsies from 98 patients with AILD-PTCLep showed that AILD-PTCLep and LeL share certain features, but there are also differences between the two. A finding common to both lymphomas was the mixture of neoplastic T-lymphocytes and a large number of epithelioid cells, which accumulated mostly in small, poorly defined clusters. Additionally, typical Sternberg-Reed and Hodgkin cells as well as giant cells resembling them were observed only rarely in either of these lymphomas. In contrast to LeL, AILD-PTCLep showed a great increase in follicular dendritic cells, which were sometimes identifiable in routine slides as so-called burned-out germinal centers. In AILD-PTCLep, the number of small vessels (predominantly epithelioid venules) and fibers is also usually greatly increased, whereas in LeL this is not the case, or the increase is only slight. Hypocellular and lymphocyte-depleted areas and PAS-positive intercellular material were seen in AILD-PTCLep (18% and 34%, respectively), but not in LeL. Large numbers of eosinophils, plasma cells and plasma cell precursors, and diffuse neoplastic infiltration of the capsule and extranodal tissue were observed much more commonly in AILD-PTCLep. Corresponding to these differences in the histologic pictures are differences in the clinical pictures. Hyperimmune phenomena (pruritus, skin rash, hemolytic anemia, allergy to antibiotics) and hypergammaglobulinemia were much more common in AILD-PTCLep than in LeL. Allergy to chemotherapeutic agents was observed only in AILD-PTCLep patients. Carcinomas were observed as a second neoplasm in 11% of the patients with AILD-PTCLep, but not at all in LeL. The similarities between the two lymphomas include the age and sex distribution (peak in the seventh decade and slight predominance of the male sex) and a similar median survival time. Another similarity is the possibility that the disease will develop into a large-cell malignant lymphoma. This was observed in 13% of the cases of AILD-PTCLep and 8% of the cases of LeL.

Epithelium↗
PubMed1989

Cytohistologic and immunohistochemical findings in Hodgkin's disease, mixed cellularity type, with a high content of epithelioid cells.

We studied 123 lymph node biopsies from 99 patients with Hodgkin's disease, mixed cellularity type, with a high content of epithelioid cells (HDMCep), by light microscopy using conventional histologic and immunohistochemical techniques. The cellular composition and histologic structure, which are described in detail, serve as a basis for discriminating HDMCep from similar lymphomas with a high content of epithelioid cells, especially from lymphoepithelioid cell lymphoma (Lennert's lymphoma, LeL) and angioimmunoblastic (LgX) type of peripheral T-cell lymphoma with a high content of epithelioid cells (AILD-PTCLep). In all lymph nodes from patients with HDMCep, the nodal architecture was effaced. In 11% it was partially replaced by a massive infiltration of epithelioid cells and small to medium-sized lymphoid cells occurring in varying proportions with some immunoblasts. In all biopsy specimens, some typical Sternberg-Reed (SR) and Hodgkin (H) cells were found. Plasma cells and plasma cell precursors were present in all biopsy specimens; in most cases, they were sparse to moderate in number. Eosinophils were always present; half of the biopsy specimens had rather large numbers of them. Formation of granulomas like those seen in sarcoidosis was noted in 7% of the specimens. Increased vascularity and an increased number of fibers were found in 53% and 63% of the biopsy specimens, respectively. Necrosis was seen in 20% of the specimens. Immunohistochemically in 30 of 67 (45%) biopsy specimens, giant cells stained positively for the granulocyte-specific monoclonal antibody 3C4 (approximately CD15). Plasma cells and plasma cell precursors in all 70 specimens exhibited a polyclonal Ig pattern. A comparison of the main clinical and laboratory data in these three entities reveals both similarities and differences. HDMCep--defined as a special variant of Hodgkin's disease, mixed cellularity type (HDMC)--marks apparently the border between Hodgkin's disease and non-Hodgkin's lymphomas.

Cytological Techniques↗