Elena Tsanou

Increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas.

There is increasing evidence that bcl6 and CD10 expression may be related to apoptosis and cell cycle progression. Therefore, 79 cases of de novo diffuse large B-cell lymphomas were studied for the expression of bcl6 and CD10 proteins in relation to 1) the apoptotic index; 2) the proliferation-associated proteins Ki67, cyclin A, and cyclin B1; and 3) the expression of the bcl2, p53, Rb, p16, and p27 proteins. Expression of bcl6, CD10, and bcl2 proteins was found in 54/79 (68%), 28/79 (35%), and 47/74 (63%) cases, respectively. The bcl6/CD10 patterns were as follows: bcl6+/CD10+ (26 cases, 32%), bcl6+/CD10- (28 cases, 33%), bcl6−/CD10− (23 cases, 31%), and bcl6−/CD10+ (2 cases, 4%). Significant positive correlations were found between bcl6/Ki67 (r = .328, P = .003), bcl6/cyclin A (r = .265, P = .018), bcl6/apoptotic index (r = .327, P = .010), CD10/Ki67 (r = .296, P = .008), and CD10/apoptotic index (r = .397, P = .001). In addition, high expression of bcl6 showed significant correlation with negative (null/low) bcl2 expression (χ2 test, P = .002). The above findings indicate that increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. The association between increased bcl6 expression and enhanced apoptosis might be due, at least in part, to the null/low bcl2 expression because previous in vitro data showed that bcl6 overexpression induces apoptosis accompanied by bcl2 and bcl-xl downregulation. Moreover, significant correlation was found between increased apoptotic index and the bcl6+/CD10+ pattern (t test: P = .014, Mann-Whitney test: P = .046). This finding and the positive correlation of the apoptotic index with bcl6 and CD10 expression may be related to previous results showing that the expression of these proteins has favorable effects on the clinical outcome of diffuse large B-cell lymphomas.

Immunohistochemical study of extracellular matrix components in epiretinal membranes of vitreoproliferative retinopathy and proliferative diabetic retinopathy

Purpose The migration, proliferation, differentiation, and adhesion of cells and other cellular functions are influenced by the surrounding extracellular matrix in normal and wound healing conditions. The formation of epiretinal membranes, a wound healing process, is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In the present study, the authors investigated the expression of various extracellular matrix components and in particular tenascin, fibronectin, laminin, collagen IV, and MMP-3 glycoprotein as well as the expression of glial fibrillary acidic protein in each type of epithelial membrane in order to elucidate the role of these molecules in the formation of these two types of membranes. Methods The authors performed immunohistochemistry in 14 PVR and 14 PDR membranes, using antibodies against the above mentioned extracellular matrix components. Tenascin and fibronectin were observed as major components in the extracellular matrix, while laminin and collagen type IV were detected as minor components in both types of membranes. A higher fibronectin expression in PVR compared with PDR membranes was found (p=0.0035). A positive relationship of its expression with the proliferative activity (p=0.15) and collagen type IV expression (p<0.0001) was also observed. Results Tenascin expression was positively correlated with glial fibrillary acidic protein positive cells in PDR membranes (p=0.04). Collagen type IV localized around vessels was observed with high levels in PDR membranes (p=0.0031). Conclusions The results indicated that the extracellular matrix components seem to be involved in PVR and PDR, contributing to tissue remodeling and perhaps by different pathogenetic pathways, which could reflect different stages of development in these two types of membranes.

Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10±/MUM1−/CD138−: 29 cases and bcl6−/CD10+/MUM1−/CD138−: two cases) and the nongerminal center B-cell-like profile (bcl6±/CD10−/MUM1+/CD138−); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=−0.536, P<0.001 and r=−0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=−0.276, P=0.014) and bid (r=−0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

Proliferation profile of classical Hodgkin's lymphomas. Increased expression of the protein cyclin D2 in Hodgkin's and Reed-Sternberg cells

There is accumulating evidence that Hodgkins and Reed–Sternberg cells of classical Hodgkins lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkins and Reed–Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkins and Reed–Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkins and Reed–Sternberg cells.

Immunohistochemical study of angiogenesis and proliferative activity in epiretinal membranes

Formation of epiretinal membranes (ERMs) is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In this study, our goal was to (i) calculate the microvessel density (MVD), (ii) evaluate vascular endothelial growth factor (VEGF) expression and (iii) correlate angiogenesis with the proliferative activity as expressed by the expression of Ki67 marker, in both membrane types.

Mucinous breast carcinoma presenting as Paget's disease of the nipple in a man: A case report

IntroductionMale breast cancer is rare compared to its female counterpart representing less than 1% of cancer in men. Moreover, mucinous carcinoma of the male breast is an extremely rare histological subtype of malignancy. Pagets disease of the nipple is rarely observed in males.Case reportHerein, we describe a unique case of an 86 years old man with mucinous breast cancer presenting as Pagets disease of the nipple. According to the immunohistochemical evaluation the neoplastic cells were positive for estrogen (ER) and progesterone receptors (PR).ConclusionTo our best knowledge this is the first case of mucinous male breast cancer presenting as Pagets disease of the nipple.

Primary mantle cell lymphoma of the conjunctiva: a case report.

Primary non-Hodgkin’s lymphomas of the conjunctiva are uncommon. They are almost exclusively extranodal marginal zone B-cell lymphomas/mucosa-associated lymphoid tissue lymphomas. In this study, we report an extremely rare case of conjunctival mantle cell lymphoma in a 78-year-old man, presenting as a unilateral epibulbar mass.

Juvenile idiopathic arthritis-associated uveitis: Data from a region in western Greece

Objective To evaluate the characteristics and visual prognosis of juvenile idiopathic arthritis-associated uveitis (JIA). Methods A retrospective review was performed on 56 patients who met the criteria for JIA to identify those with uveitis and related complications. Patients were referred to and were examined in the Pediatric Department of the University Hospital of Ioannina, between 1995 and 2007. Results The prevalence of JIA-associated uveitis was high. Despite this and the related complications, the final visual outcome was satisfactory in the majority of the cases. Authors did not observe any correlation between prognosis and sex, age at the onset of uveitis or arthritis, pattern of arthritis, or positivity for antinuclear antibodies (ANA). Conclusion We found a remarkably high prevalence of uveitis and related ocular complications in 7 (28%) of the patients, and the rate of poor visual outcome was 12%.

Contrast Sensitivity in Patients with Beta-Thalassemia Major and Sickle Cell Disease Under Regular Transfusions and Treatment with Desferrioxamine

Purpose: Evaluation of contrast sensitivity in patients with beta-thalassemia major and sickle cell disease which undergo regular transfusions and chelation therapy with desferrioxamine (DFX). Materials and Methods: We studied contrast sensitivity in 48 eyes (24 patients) with beta-thalassemia major (group A) and in 42 eyes (21 patients) with sickle cell disease (group B), compared to 60 eyes of 30 healthy individuals (control group). Contrast sensitivity was measured using B-VAT II-SG Mentor Video Aquity Tester. Results: We found no statistically significant difference between group A and group B in any spatial frequency, while we found statistically significant differences between group B and control group in all spatial frequencies studied. Between group A and control group we found statistically significant differences in spatial frequencies of 2.3, and 6 cyc/deg. Conclusion: DFX causes retinal alterations that may explain reductions in contrast sensitivity function and justifies regular evaluations that may allow early detection of visual function deterioration.

Findings of an experimental study in a rabbit model on posterior capsule opacification after implantation of hydrophobic acrylic and hydrophilic acrylic intraocular lenses

Purpose Study on cell growth on the posterior capsule after implantation of hydrophobic acrylic (Acrysof SA 60 AT) and hydrophilic acrylic (Akreos Disc) intraocular lenses (IOL) in a rabbit model and comparison of posterior capsule opacification (PCO). Methods Phacoemulsification was performed in 22 rabbit eyes, and two different IOL types (Acrysof SA60 AT and Akreos Disc) were implanted. These IOLs had the same optic geometry (square edged) but different material and design. Central PCO (CPCO), peripheral PCO (PPCO), Sommering’s ring (SR) formation, type of growth, extension of PCO, cell type, inhibition, and fibrosis were evaluated three weeks after surgery. Histological sections of each globe were prepared to document the evaluation of PCO. Results No statistically significant difference was observed between a hydrophobic acrylic IOL and a hydrophilic acrylic IOL in relation to the CPCO, PPCO, type of growth, extension, cell type, inhibition, and fibrosis. Statistically significant difference was observed in relation to the formation of SR with Acrysof SA 60 AT group presenting more SR than Akreos Disc group. Conclusion PCO was not influenced by the material of the IOL or the design of the haptics of the IOLs we studied.