Penelope Korkolopoulou

Laiko Hospital, Athínai, Attica, Greece

Are you Penelope Korkolopoulou?

Claim your profile

Publications (118)399.06 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although epigenetic alterations play an essential role in gliomagenesis, the relevance of aberrant histone modifications and the respective enzymes has not been clarified. Experimental data implicates histone H3 lysine (K) methyltransferases SETDB1 and SUV39H1 into glioma pathobiology, whereas linker histone variant H1.0 and H4K20me3 reportedly affect prognosis. We investigated the expression of H3K9me3 and its methyltransferases along with H4K20me3 and H1x in 101 astrocytic tumors with regard to clinicopathological characteristics and survival. The effect of SUV39H1 inhibition by chaetocin on the proliferation, colony formation and migration of T98G cells was also examined. SETDB1 and cytoplasmic SUV39H1 levels increased from normal brain through low-grade to high-grade tumors, nuclear SUV39H1 correlating inversely with grade. H3K9me3 immunoreactivity was higher in normal brain showing no association with grade, whereas H1x and H4K20me3 expression was higher in grade 2 than in normal brain or high grades. These expression patterns of H1x, H4K20me3 and H3K9me3 were verified by Western immunoblotting. Chaetocin treatment significantly reduced proliferation, clonogenic potential and migratory ability of T98G cells. H1x was an independent favorable prognosticator in glioblastomas, this effect being validated in an independent set of 66 patients. Diminished nuclear SUV39H1 expression adversely affected survival in univariate analysis. In conclusion, H4K20me3 and H3K9 methyltransferases are differentially implicated in astroglial tumor progression. Deregulation of H1x emerges as a prognostic biomarker.
    PLoS ONE 01/2015; 10(1):e0115101. DOI:10.1371/journal.pone.0115101 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2). Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain. Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration. We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.
    Histology and histopathology 12/2014; · 2.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: Leiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas. Methods: Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography. Results: Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient's group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues. Conclusions: This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.
    Clinical Chemistry and Laboratory Medicine 12/2014; DOI:10.1515/cclm-2014-0798 · 2.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastric involvement is unusual in primary mediastinal large B-cell lymphoma (PMLBCL), which has not yet been adequately studied. The aim of this retrospective study was to investigate the frequency of gastric involvement in 204 consecutive patients with PMLBCL that presented at 23 hospitals in Greece. Two out of 204 patients (1.0%) had gastric involvement at presentation. The first patient had symptomatic gastric disease manifested as upper gastrointestinal (GI) hemorrhage, which was the presenting symptom (first case reported in the literature). The second patient underwent positron emission tomography/computed tomography (PET/CT) at baseline staging which revealed abnormal gastric uptake. Histological examination revealed discordant lymphomatous involvement (MALT lymphoma, in a 33-year old female). The estimated frequency of gastric involvement by conventional staging was 1/204 (0.49%), but no cases were identified among asymptomatic patients. Among asymptomatic patients who underwent PET/CT at baseline staging, the PET/CT-based frequency of gastric involvement was 7.1%, but lymphomatous gastric involvement was discordant. Finally, the frequency of gastric involvement in primary progressive or relapsed disease was 2.2%. Our study shows that gastric involvement is uncommon but can be seen in different clinical settings at presentation or at progression/relapse of PMLBCL. PET/CT-based staging may provide more accurate information regarding the true incidence of sub-clinical gastric involvement in this entity, but histological confirmation is essential in order to confirm the diagnosis.
    Anticancer research 11/2014; 34(11):6717-23. · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) is an indolent lymphoma arising in extranodal sites. Several infectious agents and autoimmune disorders have been implicated in its pathogenesis. The stomach represents the most common and best-studied organ involved by MALT lymphoma and its development is strongly associated with Helicobacter pylori (Hp) infection. MALT lymphomas are characterized by an indolent clinical course and excellent survival in most cases, independently of the treatment delivered. Recent progress in the knowledge of the etiology and the cellular and molecular pathological events related to MALT lymphomas allowed us to improve our clinical understanding of this disease entity and to better define treatment strategies.
    Current Hematologic Malignancy Reports 09/2014; 9(3). DOI:10.1007/s11899-014-0218-1
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) is a premalignant condition characterized by the presence of less than 5000/μL circulating clonal B cells in otherwise healthy individuals. Three subcategories have been identified according to the immunophenotypic features: CLL-like, CD5(+) atypical, and CD5(-) MBL. CLL-like MBL is by far the most frequent and best studied category and further divided in low-count [LC] and high-count [HC] MBL, based on a cutoff value of 500/μL clonal B cells. LC-MBL typically remains stable and probably does not represent a truly premalignant condition, but rather an age-related immune senescence. On the other hand, HC-MBL is closely related to CLL-Rai0, bearing similar immunogenetic profile, and is associated with an annual risk of progression to CLL requiring therapy at a rate of 1.1%. Currently there are no reproducible factors for evaluating the risk of progression to CLL. CD5(-) MBL is characterized by an immunophenotype consistent with marginal zone origin and displays many similarities with marginal zone lymphomas (MZL), mainly the splenic MZL. The cutoff value of 5000/μL clonal B cells cannot probably be applied in CD5(-) MBL, requiring a new definition to describe those cases.
    BioMed Research International 09/2014; 2014:258917. DOI:10.1155/2014/258917 · 2.71 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Deregulated signalling through phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I-IV in relation to clinicopathological features. Increased p-AKT expression correlated with poor prognosis in plaques (P=0.0198), whereas p-AKT was an independent predictor of poor survival in the entire cohort (P=0.017, HR=1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages (P=0.0744). Molecular analysis showed no AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease (P=0.0253) and progression (P<0.0001) free survival in tumour stage. Although activation of PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients' prognosis with tumours.
    Experimental Dermatology 09/2014; 23(12). DOI:10.1111/exd.12547 · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the significance of PI3K/AKT/mTOR pathway and its interactions with MAPK, JAK/STAT and Notch pathways in meningioma progression. Paraffin-embedded tissue from 108 meningioma patients was analysed for the presence of mutations in PIK3CA and AKT1. These were correlated with the expression status of components of the PI3K/AKT/mTOR pathway, including p85α and p110γ subunits of PI3K, phosphorylated (p)-AKT, p-mTOR, p-p70S6K and p-4E-BP1, as well as of p-ERK1/2, p-STAT3 and Notch-1, clinicopathological data and patient survival. A mutation in PIK3CA or AKT1 was found in around 9 % of the cases. Higher grade meningiomas displayed higher nuclear expression of p-p70S6K; higher nuclear and cytoplasmic expression of p-4E-BP1 and of Notch-1; lower cytoplasmic expression of p85αPI3K, p-p70S6K and p-ERK1/2; and lower PTEN Histo-scores (H-scores). PTEN H-score was inversely correlated with recurrence probability. In univariate survival analysis, nuclear expression of p-4E-BP1 and absence of p-ERK1/2 expression portended adverse prognosis, whereas in multivariate survival analysis, p-ERK1/2 expression emerged as an independent favourable prognostic factor. Treatment of the human meningioma cell line HBL-52 with the PI3K inhibitor LY294002 resulted in reduction of p-AKT, p-p70S6K and p-ERK1/2 protein levels. The complex interactions established between components of the PI3K/AKT/mTOR pathway, or with components of the MAPK, JAK/STAT and Notch-1 pathways, appear to be essential for facilitating and fuelling meningioma progression.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2014; 465(4). DOI:10.1007/s00428-014-1641-3 · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student t test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log-rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR=1.016, p=0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p=0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2014; 136(7). DOI:10.1002/ijc.29140 · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity represents a route to broad physiological dysfunction affecting major organs including male urogenital system. Hyperglycemia, hyperlipidemia, and oxidative stress associated with obesity augment the formation of reactive metabolic by-products, namely advanced glycation end products (AGEs), leading to increased tissue deposition and damage. The exogenous intake and the endogenous accumulation of AGEs contribute to metabolic and reproductive abnormalities in both women and men. The present study assessed the effects of a diet high in saturated fatty acids (SAFA) on the lipid and metabolic profile (AGE levels, oxidative stress) as well as pathogenic (AGE, receptor for AGEs [RAGE] expression, apoptosis) and morphometric parameters of male reproductive system in vivo. Effects of switching to a diet rich in monounsaturated fatty acids (MUFA) or equal in the proportion MUFA to SAFA were further investigated. SAFA-fed animals were characterized by increased serum lipid concentrations (p < .05) compared to controls, but AGEs and peroxide levels were not significantly different across the different experimental groups. Elevated AGE deposition was detected for the first time in germ cells with a higher staining intensity in animals on the SAFA diet, compared to MUFA or MUFA-SAFA-fed animals or the control samples (p = .018). In Leydig cells, AGE localization was higher in the entire cohort of high-fat-fed animals compared to controls (p < .05). High-fat-fed mice displayed enhanced apoptosis compared to controls (p < .005). Furthermore, prostatic tissue demonstrated reduction in epithelial folding, an effect which was significantly reversed after MUFA diet administration. Our findings provide the basis for further investigation of AGE-RAGE axis in testicular and prostatic disturbances associated with diet-induced obesity. Simple dietetic intervention has beneficial effects on metabolic dysfunction of reproductive system before overt manifestations, indicating glycation as a promising therapeutic target.
    Experimental Biology and Medicine 05/2014; 239(8). DOI:10.1177/1535370214531899 · 2.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalyzing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. The present study investigated the potential association of p16(INK) (4A) promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation-specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki-67 index), p16(INK) (4A) and SETDB1 expression were evaluated by immunohistochemistry. High-frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (p=0.0514). p16(INK) (4A) promoter methylation was higher in vertical growth phase (60%) melanomas than in radial (40%, p=0.063) and those displaying epidermal involvement (p=0.046). Importantly, p16(INK) (4A) methylation correlated with increased melanoma thickness according to Breslow index (p=0.0495) and marginally with increased Clark level (I/II vs III/IV/V, p=0.070). Low (1-30%) p16(INK) (4A) expression was detected at the majority (19/54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (p=0.078). SETDB1 nuclear immunoreactivity was observed in 47/57 (82.46%) cases, whereas 27/57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16(INK) (4A) methylation and p16(INK) (4A) expression (p=0.033, p=0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0-5/mm(2) vs >5/mm(2) , p=0.0869), advanced Clark level (III-V, p=0.0380), epidermal involvement (p=0.0331) and the non-chronic sun exposure associated melanoma type (p=0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16(INK) (4A) promoter and several prognostic parameters in melanomas. This article is protected by copyright. All rights reserved.
    Experimental Dermatology 03/2014; 23(5). DOI:10.1111/exd.12398 · 4.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-alpha resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC. In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-kappaBeta (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases. Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis. Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia.
    BMC Cancer 03/2014; 14(1):149. DOI:10.1186/1471-2407-14-149 · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis leads to new blood vessel formation and is implicated in both physiological and pathological situations. The vascular endothelial growth factor (VEGF) family is the major mediator of this process. The aim of our study was to evaluate the expression of VEGF-A, vascular endothelial growth factor receptor-1 (VEGFR-1) and VEGFR-2 and their correlation with clinicopathological parameters and prognosis in patients with classical Hodgkin lymphoma (cHL), since the role of angiogenesis in this tumor still remains unclear. The immunohistochemical expression of VEGF-A, VEGFR-1 and VEGFR-2 was examined in 194 patients with cHL. The neoplastic Hodgkin Reed–Sternberg (HRS) cells expressed VEGF-A, VEGFR-1 and VEGFR-2 in 90.3%, 97.2% and 94.1% of cases, respectively. Only the expression of VEGFR-2 was positively correlated with serum albumin levels ≥ 4 g/dL. No correlation with patient outcome was observed. All three molecules were statistically correlated with ramifications of blood vessels. Summarizing, our results are not sufficient to consider VEGF-A and/or VEGF receptors as prognosticators in cHL.
    Leukemia and Lymphoma 03/2014; 55(3). DOI:10.3109/10428194.2013.813629 · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in ∼40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereasIL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients.
    BioMed Research International 01/2014; 2014:251479. DOI:10.1155/2014/251479 · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mastocytosis is a myeloproliferative neoplasm characterized by clonal expansion of abnormal mast cells, ranging from the cutaneous forms of the disease to mast cell leukemia. In a significant proportion of patients, systemic mastocytosis (SM) coexists with another hematologic malignancy, termed systemic mastocytosis with an associated hematologic nonmast cell lineage disorder (SM-AHNMD). Despite the pronounced predominance of concomitant myeloid neoplasms, the much more unusual coexistence of lymphoproliferative diseases has also been reported. Imatinib mesylate (IM) has a role in the treatment of SM in the absence of the KITD816V mutation. In the setting of SM-AHNMD, eradicating the nonmast cell malignant clone greatly affects prognosis. We report a case of an adult patient with SM associated with B-lineage acute lymphoblastic leukemia (B-ALL). Three cases of concurrent adult ALL and mastocytosis have been reported in the literature, one concerning SM and two concerning cutaneous mastocytosis (CM), as well as six cases of concomitant CM and ALL in children.
    Case Reports in Medicine 01/2014; 2014:526129. DOI:10.1155/2014/526129
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Castleman's disease is a benign lymphoproliferative condition with three distinct histological subtypes. Clinically it presents in either a unicentric or multicentric manner and can affect various anatomic regions, the mediastinum being the most frequent location. We herein present a rare case of unifocal retroperitoneal mass proved to be hyaline vascular Castleman's disease. We perform a review of the current literature pertaining to such lesions, focusing on the management of the various clinical and histological variants of the disease. Surgical excision is the treatment of choice for unifocal Castleman's disease.
    01/2014; 2014:643746. DOI:10.1155/2014/643746
  • [Show abstract] [Hide abstract]
    ABSTRACT: The biological and clinical significance of a clonal B-cell lymphocytosis with an immunophenotype consistent with marginal zone origin (CBL-MZ) is poorly understood. We retrospectively evaluated 102 such cases with no clinical evidence to suggest a concurrent MZ lymphoma. Immunophenotyping revealed a clonal B-cell population with Matutes score ≤2 in all cases; 19/102 were weakly CD5-positive and all 35 cases tested expressed CD49d. Bone marrow biopsy exhibited mostly mixed patterns of small B-lymphocytic infiltration. 48/66 (72.7%) cases had an abnormal karyotype. Immunogenetics revealed overusage of the IGHV4-34 gene and somatic hypermutation in 71/79 (89.8%) IGHV-IGHD-IGHJ gene rearrangements. With a median follow-up of 5 years, 85 cases remain stable (Group A), whereas 17 cases (Group B) progressed, of whom 15 developed splenomegaly. Neither the clonal B-cell count, degree of marrow infiltration, immunophenotypic nor immunogenetic findings at diagnosis distinguished between the 2 groups. However deletions of chromosome 7q were confined to Group A and complex karyotypes were more frequent in Group B. Although CBL-MZ may antedate SMZL/SLLU, most cases remain stable over time. These cases, not readily classifiable within the WHO classification, raise the possibility that CBL-MZ be considered as a new provisional entity within the spectrum of clonal marginal zone disorders.
    Blood 12/2013; DOI:10.1182/blood-2013-07-515155 · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the prevalence of autoimmune gastritis, Enterochromaffin-like cell (ECL-cell) hyperplasia and Gastric Neuroendocrine tumours type 1 (GNET1) in patients with autoimmune thyroid disease. Prospective observational study in a single institutional study. 120 patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Clinic. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up 37.5±14.4months. Autoimmune gastritis was defined by the presence of anti-parietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured. 111 patients had Hashimotos' thyroiditis and 9 Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimotos' thyroiditis, 2 with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15/40 (37.5%). Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7/40 (17.5%)]. Only increased gastrin (p=0.03) levels predicted the presence ECL-cell hyperplasia. A GNET1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up. Concomitant autoimmune gastritis was found in 33.3% of patients with autoimmune thyroid disease, 17.5% of whom had ECL-cell hyperplasia that evolved to GNET1 in one (2.5%). Larger studies with longer follow-up are needed to define the incidence of GNET1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 10/2013; 80(5). DOI:10.1111/cen.12346 · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is upregulated in a number of human cancers, including non-small cell lung cancer (NSCLC). Its potential role in NSCLC progression provides an attractive target for anticancer therapy. The expression of phosphorylated mTOR (p-mTOR), phosphorylated AKT (p-AKT), p85α and p110γ subunits of PI3K, phosphorylated p70S6K (p-p70S6K), phosphatase and tensin homolog (PTEN) and phosphorylated 4E-BP1 (p‑4E‑BP1) was examined by immunohistochemistry in 102 NSCLC specimens. The results were correlated with clinicopathological features. We also examined 61 of our cases for the presence of PIK3CA, AKT1, PTEN and K-RAS mutations. A common PIK3CA mutation was detected at exon 9 in 2 samples (p.E545K), whereas another sample displayed a rare mutation (p.D1018N). Furthermore, 10 out of 54 cases (18.5%) had a K-RAS mutation at codon 12, 5 had a PTEN mutation (exons 7 and 8) and 1 case had an AKT1 mutation (p.E17K). PTEN mutations were associated with nodal metastases. The expression of p-mTOR positively correlated with that of p-AKT and p-p70S6K and was higher in adenocarcinomas along with nuclear p110γPI3K expression, whereas p-4E-BP1 expression was higher in squamous cell carcinomas. We also established a positive association between p85αPI3K or p110γPI3K and cytoplasmic p-AKT and its downstream effectors. An inverse correlation was noted between p-4E-BP1 immunoexpression and tumour status and nuclear p-AKT expression as regards tumour stage. Univariate survival analysis demonstrated that p-4E-BP1 expression, either alone or in combination with cytoplasmic p-AKT expression had an adverse prognostic significance in adenocarcinomas. The combination of p-4E‑BP1 and cytoplasmic p-AKT expression remained significant in the multivariate analysis as a function of their interaction with histological type. Our data demonstrate the significance of p‑4E‑BP1 immunoexpression as a molecular marker of prognostic value in adenocarcinomas, particularly when combined with p-AKT.
    Oncology Reports 05/2013; 30(2). DOI:10.3892/or.2013.2512 · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT We have analyzed the immunohistochemical expression of a wide range of molecules, along with the proliferation rate separately in the proliferation centers (PCs) and in the rest of tumor area on lymph node or spleen sections of CLL patients. Fas, FasL and c-FLIP were observed both within and outside the PCs in all cases. However only the difference in FasL expression between the PCs and the non-PC areas attained statistical significance. Median survivin expression in the PCs was higher compared to the non-PC areas. Cleaved-caspase 3 was expressed in very low levels both within and outside PCs while the BCL-2 protein was expressed in high levels in all cases in both tumor compartments. Multivariate analysis demonstrated that concurrent overexpression of Fas/FasL/c-FLIP in the PCs was correlated with worse outcome for progression free survival as well as for overall survival.
    Leukemia & lymphoma 05/2013; 55(3). DOI:10.3109/10428194.2013.806802 · 2.61 Impact Factor

Publication Stats

2k Citations
399.06 Total Impact Points

Institutions

  • 2008–2015
    • Laiko Hospital
      Athínai, Attica, Greece
  • 2014
    • Society for Experimental Biology & Medicine
      Society Hill, New Jersey, United States
  • 2013–2014
    • Harokopion University of Athens
      Athínai, Attica, Greece
    • University of Crete
      • School of Medicine
      Réthymnon, Kriti, Greece
  • 2005–2014
    • Athens State University
      Athens, Alabama, United States
  • 2001–2014
    • National and Kapodistrian University of Athens
      • • Division of Pathophysiology
      • • Department of Medicine
      • • Division of Internal Medicine II
      • • Faculty of Medicine
      Athínai, Attica, Greece
    • Γενικό Νοσοκομείο Ασκληπιείο Βούλας
      Βούλα, Attica, Greece
  • 2012
    • Athens Medical Center
      Athínai, Attica, Greece
  • 2006–2009
    • University of Kuopio
      Kuopio, Eastern Finland Province, Finland
  • 2000–2001
    • National Technical University of Athens
      Athínai, Attica, Greece
  • 1993
    • University of Piraeus
      Le Pirée, Attica, Greece