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ABSTRACT: : To investigate the expression of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and osteoprotegerin (OPG) in bladder urothelial carcinomas (UCs) and assess possible interrelations with other regulators of TRAIL induced apoptosis (p65/NF-κB, p-ERK1/2, p-AKT) and FGFR3, as well as to elucidate their potential involvement in bladder tumourigenesis and determine their potential prognostic utility.
: Paraffin embedded transurethral resection tissue from 128 patients with UC was immunostained for TRAIL and OPG as well as for p65/NF-κB, p-ERK1/2, p-AKT and FGFR3.
: TRAIL and OPG were coexpressed in 96.6% of cases and positively interrelated. OPG expression was significantly different among histological grades, being higher in low-grade UCs and was inversely correlated with the presence of lymphovascular invasion (LVI). TRAIL also displayed an inverse relationship with histological grade, T-category and LVI. Both OPG and TRAIL expression were positively correlated with FGFR3 expression, the former relationship being marginal. Moreover, increased TRAIL expression was marginally correlated with lower NF-κB/p65 nuclear expression. Increased OPG expression adversely affected survival both in univariate and multivariate analysis.
: OPG and TRAIL are frequently expressed and coexpressed in UCs, supporting the involvement of OPG in the resistance to TRAIL-driven apoptosis. Inhibition of NF-κB activation may also play a similar role, although less important. OPG emerged as an independent prognostic marker of adverse significance.
Pathology 02/2013; 45(2):138-44. · 2.38 Impact Factor
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Christina Kalpadakis,
Gerassimos A Pangalis,
Maria K Angelopoulou,
Sotirios Sachanas,
Flora N Kontopidou,
Xanthi Yiakoumis,
Stella I Kokoris,
Evagelia M Dimitriadou,
Maria N Dimopoulou,
Maria Moschogiannis, Penelope Korkolopoulou,
Marie-Christine Kyrtsonis,
Marina P Siakantaris,
Theodora Papadaki,
Panayiotis Tsaftaridis,
Eleni Plata,
Helen E Papadaki,
Theodoros P Vassilakopoulos
[show abstract]
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ABSTRACT: Background. Treatment of splenic marginal zone lymphoma (SMZL) patients is not standardized. Recent data suggest that rituximab is highly effective and could be considered as initial therapy.Aim. To assess the efficacy of rituximab monotherapy in a large series of patients with SMZL and compare these results with splenectomy results.Methods. The studied population included 85 patients. Fifty-eight received rituximab at a dose of 375 mg/m(2) per week for 6 weeks as induction followed by maintenance at the same dose every 2 months for 1-2 years, whereas 27 patients were treated using splenectomy only.Results. The overall response rate to rituximab 2 months after the end of induction was 95% (complete response [CR], 45%; unconfirmed CR, 26%; partial response, 24%). The median times to hematologic and clinical response were 2 weeks and 3 weeks, respectively. Forty-three of 55 patients already completed the maintenance phase: 28 sustained their initial response, 14 improved their response, and one progressed. Eighty-five percent of splenectomized patients responded, and two were treated with rituximab as consolidation after splenectomy and achieved a CR. The 5-year overall and progression-free survival (PFS) rates for rituximab-treated and splenectomized patients were 92% and 77% (p = .09) and 73% and 58% (p = .06), respectively. Furthermore, maintenance therapy with rituximab resulted in a longer duration of response (at 5 years, PFS was 84% for patients receiving maintenance and 36% for patients without maintenance, p <.0001).Conclusions. Rituximab is a very effective and well-tolerated therapy and may be substituted for splenectomy as the first-line treatment of choice for patients with SMZL.
The Oncologist 01/2013; · 3.91 Impact Factor
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Penelope Korkolopoulou,
Georgia Levidou,
Eleni-Andriana Trigka,
Niki Prekete,
Maria Karlou,
Irene Thymara,
Stratigoula Sakellariou,
Paraskevi Fragkou,
Dimitrios Isaiadis,
Petros Pavlopoulos,
Efstratios Patsouris,
Angelica A Saetta
[show abstract]
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ABSTRACT: What's known on the subject? and What does the study add? A few published studies investigating single or various PI3K/AKT/mTOR signalling components have produced inconsistent results. Moreover, PI3K regulatory subunit p85a and activated p70S6K expression levels have not been previously examined in urothelial carcinoma (UC). The present study addresses simultaneously all key members of PI3K/AKT/mTOR signalling cascade supporting a differential implication of PI3K/AKT/mTOR pathway components in urothelial tumorigenesis. Furthermore, we propose p-4E-BP1 as a potential prognostic marker in UC, which might assist the selection of patients more likely to benefit from chemotherapy regimens based on PI3K/AKT/mTOR pathway inhibition. Finally, the present study indicates PIK3CA/AKT1 mutational status as a potential predictive marker for time-to-recurrence. OBJECTIVE: • To perform a comprehensive simultaneous assessment of all key members of phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway along with AKT homolog 1 (AKT1) and PIK3 catalytic alpha polypeptide (PIK3CA) mutations in bladder urothelial carcinoma (UC). • Published information is limited to a few studies looking into single or various combinations of members of this pathway with inconsistent results. In particular the expression status of phosphorylated (p-)p70S6 kinase (p70S6K) and p85a subunit of PI3K has not been tested in UC. PATIENTS AND METHODS: • Paraffin-embedded transurethral resection tissue from 113 patients with UC was investigated for the association of p85aPI3K, p-AKT, p-mTOR, p-p70S6K and p-4E-BP1 (eukaryotic initiation factor 4E-binding protein 1) expression status, as well as PIK3CA and AKT1 mutations with p-extracellular signal-regulated kinase 1/2 (ERK1/2), fibroblast growth factor receptor 3 (FGFR3), pathological features, recurrence and cancer-specific survival. RESULTS: • With the exception of p-p70S6K, all others components of the PI3K/AKT/mTOR pathway were upregulated in UCs as compared with normal urothelium. • p-mTOR expression strongly correlated with its upstream p-AKT and marginally with its downstream p-p70S6K. p85aPI3K and p-ERK1/2 levels were also marginally correlated. • PIK3CA and AKT1 mutations were distinctly uncommon and mutually exclusive, without any association with pathological features. However, the presence of AKT1 mutations was associated with increased FGFR3 levels and was restricted to p85aPI3K immunonegative cases, whereas PIK3CA mutant cases had marginally lower p85aPI3K levels. • The presence of PIK3CA single or combined with AKT1 mutations was associated with shorter recurrence-free survival in univariate survival analysis. An inverse relationship was established between p-4E-BP1 immunopositivity and histological grade or T category, as well as between p-p70S6K levels and T category, the latter relationship being of marginal significance. • p-4E-BP1 nuclear expression was marginally associated with the presence of lymphovascular invasion and adversely affected survival in multivariate, but not in univariate analysis. CONCLUSIONS: • PI3K/AKT/mTOR signalling components appear to be differentially implicated in urothelial tumorigenesis and, with the exception of p85aPI3K, are unrelated to the PIK3CA or AKT1 mutational status. • Our findings propose p-4E-BP1 as a potential prognostic marker in UC independent of its association with pathological features, which might assist the selection of patients more likely to benefit from PI3K/AKT/mTOR axis inhibition. • PIK3CA/AKT1 mutational status may have a place in the prediction of time-to-recurrence.
BJU International 10/2012; · 2.84 Impact Factor
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[show abstract]
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ABSTRACT: Glyoxalase detoxification system composed of glyoxalase-I and II (GLO-I, II), is ubiquitously expressed and implicated in the protection against cellular damage due to cytotoxic metabolites such as advanced glycation end-products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGEs deposition been associated either with a high AGEs diet in experimental animals or hyperandrogenic disorders like Polycystic Ovarian Syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal non-androgenized (NAN, Group A, n=18) and androgenised prepubertal (AN) rats (Group B, n=29). Both groups were further randomly assigned, either to high (HA) or low (LA) AGE content diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed with HA diet compared to LA (p=0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared to NAN (p≤0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s)=0.533, p<0.001), estradiol (r(s)=0.326, p=0.033) and progesterone levels (r(s)=0.500, p<0.001). A negative correlation was observed between GLO-I activity and AGEs expression in the ovarian granulosa cell layer of all groups with marginal statistical significance (r(s)=-0.263, p=0.07). The present data demonstrate that ovarian GLO-I activity may be regulated by dietary composition and androgen levels. Modification of ovarian GLO-I activity observed for the first time in this androgenised prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterising PCOS.
Molecular Medicine 07/2012; · 3.76 Impact Factor
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Penelope Korkolopoulou,
Georgia Levidou,
Elias A El-Habr,
Christina Piperi,
Christos Adamopoulos,
Vassilis Samaras,
Efstathios Boviatsis,
Irene Thymara,
Eleni-Andriana Trigka,
Stratigoula Sakellariou,
Nikolaos Kavantzas,
Efstratios Patsouris,
Angelica A Saetta
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[hide abstract]
ABSTRACT: To investigate the significance of the mammalian target of rapamycin (mTOR) pathway in astrocytic tumours, published information in this context being limited, especially regarding phosphorylated 4E-binding protein (p-4E-BP) 1.
Paraffin-embedded tissue from 111 patients with astroglial tumours (grades II-IV) was investigated for the association of phosphorylated mTOR (p-mTOR) signalling components with phosphorylated extracellular signal-related kinase 1/2 (p-ERK1/2) and phosphorylated AKT (p-AKT) expression, clinicopathological features, angiogenesis, isocitrate dehydrogenase 1 (IDH1)-R132H, and survival. Expression was also quantified by western blot analysis in 12 cases and in three primary glioma cell cultures following rapamycin treatment. p-mTOR expression correlated with p-4E-BP1 expression and marginally with p-p70S6K expression. p-4E-BP1 expression increased with tumour grade. Rapamycin induced a decline in phosphorylation levels of all three proteins. Nuclear p-AKT and cytoplasmic p-ERK1/2 immunoexpression correlated with p-4E-BP1 expression, whereas cytoplasmic p-AKT expression correlated with p-p70S6K expression. All three proteins were associated with increased angiogenesis but not with IDH1-R132H expression status. p-mTOR adversely affected overall and disease-free survival in univariate analysis. In multivariate survival analysis, the presence of p-4E-BP1 predicted shortened overall survival in the entire cohort and glioblastomas.
mTOR signalling components are differentially involved in the acquisition of a more aggressive and angiogenic phenotype in astrocytic tumours. Moreover, p-4E-BP1 emerges as a novel prognostic marker, which might aid in the selection of patients who are more likely to benefit from therapy with mTOR inhibitors.
Histopathology 06/2012; 61(2):293-305. · 3.08 Impact Factor
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Irina Alafuzoff,
Ellen Gelpi,
Safa Al-Sarraj,
Thomas Arzberger,
Johannes Attems,
Istvan Bodi,
Nenad Bogdanovic,
Herbert Budka,
Orso Bugiani,
Elisabet Englund, [......],
Camelia Monoranu,
Piero Parchi,
Efstratios Patsouris,
Wolfgang Roggendorf,
Annemieke Rozemuller,
Danielle Seilhean,
Nathalie Streichenberger,
Dietmar R Thal,
Stephen B Wharton,
Hans Kretzschmar
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ABSTRACT: Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies is recommended by BNE. However, a simple strategy regarding assessment of load of alteration is urgently needed to yield reproducible, and at the same time, comparable results between centres.
Experimental gerontology 06/2012; 47(11):825-33. · 3.34 Impact Factor
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ABSTRACT: Replication protein A (RPA) is an ssDNA-binding protein required for the initiation of DNA replication and the stabilization of ssDNA. Collaboration with several molecules, that is, the MCM2-7 complex, has been suggested to be imperative for its multifaceted role. In this study, we investigated the immunohistochemical expression of the RPA2 subunit in correlation with the MCM-2 and MCM-5 and Ki67 index, and assessed its prognostic significance in 76 patients with nonearly ovarian adenocarcinomas, the majority of whom had a serous histotype. RPA2 protein expression was observed in all cases, whereas the staining intensity varied from weak to strong. RPA2 expression was correlated with the tumor stage in the entire cohort and in serous tumors (P=0.0053 in both relationships). Moreover, RPA2 immunoexpression was positively correlated with MCM-2 (P=0.0001) and MCM-5 (P<0.0001) expression, but was unrelated to the Ki67 index (P>0.10). In multivariate survival analysis, RPA2 expression emerged as an independent predictor of adverse outcome (P<0.0001) along with tumor histologic grade. RPA2 remained an independent predictor of survival (P=0.002) even after adjustment for MCM-2 and MCM-5 expression and when analysis was restricted to serous carcinomas (P=0.004). Our results further support the interrelation of RPA2 protein with MCM-2 and MCM-5 in OCs. Moreover, RPA2 protein may play an important role in ovarian tumorigenesis, and may serve as a useful independent molecular marker for stratifying patients with OC in terms of prognosis.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 05/2012; 31(4):319-27. · 2.07 Impact Factor
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Sotirios G Papageorgiou,
Panayiotis Diamantopoulos,
Georgia Levidou,
Maria K Angelopoulou,
Panagiota Economopoulou,
Anna Efthimiou,
Nikos Constantinou,
Andreas Katsigiannis, Penelope Korkolopoulou,
Vassiliki Pappa, [......],
Marie-Christine Kyrtsonis,
Ioannis Kotsianidis,
Christina Kalpadakis,
Meletios-Athanassios Dimopoulos,
Photis Beris,
John Meletis,
Gerassimos A Pangalis,
John Dervenoulas,
Panayiotis Panayiotidis,
Theodoros P Vassilakopoulos
[show abstract]
[hide abstract]
ABSTRACT: Central nervous system (CNS) involvement in patients with primary mediastinal large B-cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R-CHOP ± RT in comparison to patients treated with CHOP ± RT (n = 45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R-CHOP treated patients and a 2-year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2-year actuarial incidence of 7.5% (p = 0.29). Again, both patients had isolated CNS relapses. Parenchymal-only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age-adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R-CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high-dose therapy and autologous stem cell transplantation: They are both alive and disease-free 18 and 23 months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long-term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL. Copyright © 2012 John Wiley & Sons, Ltd.
Hematological Oncology 05/2012; · 2.47 Impact Factor
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Theodoros P. Vassilakopoulos,
Gerassimos A. Pangalis,
Marina P. Siakantaris,
Georgia Levidou,
Xanthi Yiakoumis,
Charalambos Floudas,
Despina Gribabis,
Spyridon Bouros,
Ioannis Metaxas,
Evangelia M. Dimitriadou,
Lambrini Pantazi,
Catherine Tsoukala, Penelope Korkolopoulou,
Anastasios Andreopoulos,
George Vaiopoulos
[show abstract]
[hide abstract]
ABSTRACT: Kikuchi-Fujimoto disease is a form of reactive lymphadenopathy, which was firstly described in Japan, but is uncommon in the
Western world. We retrospectively reviewed the medical records of nine cases of adult or adolescent Kikuchi’s disease diagnosed
in a single Haematology Unit in Athens, Greece between 1990 and 2006. The median age of the patients was 25years (14–40)
and 8/9 were females. All patients presented with cervical lymphadenopathy sparing the supraclavicular fossa; one had associated
axillary lymphadenopathy, seven had fever and two were asymptomatic. The median duration of lymphadenopathy before presentation
was 30days (10–45). Just palpable splenomegaly was recorded in three patients. The median value of the maximal lymph node
diameter was 2cm (1–5) and only 1/9 had nodes >2cm in their largest diameter. Lymphadenopathy was tender in two patients;
hard nodes were observed in three patients. The median leukocyte count was 4.7×109/l (2.2–4.9) with a normal differential in 7/9 patients. No infectious agent could be demonstrated. One patient had clinical
and laboratory evidence of primary antiphospholipid syndrome (APLS). In conclusion, Kikuchi’s disease represents a rare but
important diagnostic possibility for patients presenting with lymphadenopathy in Greece and other western countries. In this
setting, autoimmune disorders, mainly lupus and APLS, should be considered and excluded by the appropriate laboratory work-up.
KeywordsKikuchi’s disease-Kikuchi-Fujimoto-Lymphadenopathy-Cervical-Antiphospholipid syndrome-Autoimmune disease
Rheumatology International 04/2012; 30(7):925-932. · 1.88 Impact Factor
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Georgia Levidou,
Angelica A Saetta,
Fanie Gigelou,
Maria Karlou,
Polyanthi Papanastasiou,
Angeliki Stamatelli,
Nikolaos Kavantzas,
Nikolaos V Michalopoulos,
George Agrogiannis,
Efstratios Patsouris, Penelope Korkolopoulou
[show abstract]
[hide abstract]
ABSTRACT: Colorectal (CRC) carcinogenesis through various morphological stages has been linked to several genetic and epigenetic changes. The Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates.
In this study, we investigated the presence of B-raf and K-ras mutations in 94 consecutive cases of primary colon adenocarcinoma in correlation with the immunohistochemical expression of total and activated ERK and the expression of mismatch repair proteins (MMR) hMLH1 and hMSH2 as well as their correlations with standard clinicopathological parameters.
The immunostaining pattern for total and activated ERK was nuclear and cytoplasmic. hMLH1 and hMSH2 proteins were preserved in 45/63 (71.43%) cases and 35/53 (66.04%) cases respectively. Total ERK nuclear expression, was positively correlated with tumor stage (p = 0.049), whereas nuclear pERK expression was positively correlated with histological grade (p = 0.0113) and tumor stage (p = 0.0952), although the latter relationship was of marginal significance. DNA sequencing showed that 12 samples (12.7%) had a mutation in B-RAF Exon 15 and none in Exon 11, whereas 22 (23.4%) had a K-ras mutation. Disruption of the MAP kinase pathway-either through K-ras or B-raf mutation-was detected in 37% of all the examined cases, although the overexpression of total and activated ERK1/2 was not correlated with the mutational status of K-ras or B-raf genes. Finally, the preservation of hMLH1 or hMSH2 immunoexpression was not correlated with the presence of B-raf and/or K-ras mutations.
In this study, we present evidence that ERK activation occurs in a K-ras or B-raf -independent manner in the majority of primary colon cancer cases. Moreover, B-raf mutations are not associated with mismatch-repair deficiency through loss of hMLH1 or hMSH2 expression. Activated ERK could possibly be implicated in tumor invasiveness as well as in the acquisition of a more aggressive phenotype.
World Journal of Surgical Oncology 02/2012; 10:47. · 1.12 Impact Factor
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Penelope Korkolopoulou,
Georgia Levidou,
Elias A El-Habr,
Christos Adamopoulos,
Vassilis Samaras,
Athanasios Zisakis,
Nikolaos Kavantzas,
Efstathios Boviatsis,
Paraskevi Fragkou,
Athanasios G Papavassiliou,
Efstratios Patsouris,
Christina Piperi
[show abstract]
[hide abstract]
ABSTRACT: The aim was to expand recently published information regarding the significance of the interleukin (IL)-8/p-STAT-3 (signal transducer and activator of transcription) pathway in astrocytomas, focusing on the IL-8 receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and the STAT-3 inhibitor SOCS-3 (suppressors of cytokine signaling). A total of 91 paraffin-embedded human astrocytoma tissues (grades II-IV) were investigated for the association of SOCS-3 and CXCR2 expression with clinicopathologic and morphometric microvascular characteristics, vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression and patient survival. Peripheral IL-8 secretion levels were assessed by enzyme-linked immunosorbent spot (ELISPOT). SOCS-3, p-STAT-3 and CXCR2 protein levels were also quantified by Western immunoblotting in six cases, and the protein levels of SOCS-3 and CXCR2 were correlated with the immunohistochemical expression of the respective proteins. All CXCR2-positive cases by Western immunoblotting displayed increased peripheral IL-8 secretion levels. Treatment of primary glioblastoma cell cultures with exogenous IL-8 enhanced proliferation, and this effect was inhibited by treatment with a neutralizing anti-CXCR2 antibody. SOCS-3 and CXCR2 were expressed by neoplastic astrocytes in 92.4% and 48.78% of cases, respectively, with their levels increasing with histological grade and extent of necrosis. VEGF expression and microvessel density, CXCR2 and IL-8 levels were interrelated. SOCS-3 and p-STAT-3 were co-expressed in 85.7% of cases, although they were not interrelated. In univariate survival analysis, increased SOCS-3 expression and the presence of CXCR2 adversely affected survival, whereas in multivariate analysis, only CXCR2 remained significant. The prognostic significance of CXCR2 was validated in an independent set of 63 patients. Our data implicate IL-8/CXCR2 signaling pathway in the progression and regulation of angiogenesis in astrocytomas and provide a rationale for CXCR2 therapeutic exploitation in these tumors.
Molecular Medicine 01/2012; 18(1):379-88. · 3.76 Impact Factor
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[show abstract]
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ABSTRACT: Primary thyroid lymphoma is a rare malignancy, representing 2-8% of all thyroid malignancies and 1-2% of all extranodal lymphomas. The majority of cases concern non-Hodgkin's lymphoma of B cell origin, following by Hodgkin's disease, T cell lymphomas and rarely marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. MALT lymphomas have been associated with long-standing autoimmune Hashimoto's thyroiditis. We present the case of a 44-years-old woman with thyroid MALT lymphoma in the background of multinodular goiter of autoimmune origin.
Rare tumors 01/2012; 4(1):e2.
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[show abstract]
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ABSTRACT: Astrocytomas, the most common type of gliomas, and especially grade IV glioblastomas are "endowed" with strong proliferation and invasion potentials, high recurrence rate, and poor patients' prognosis. Aberrant signaling of AKT-mTOR (mammalian target of rapamycin) has been implicated in carcinogenesis. This paper is focused on the impact of deregulated AKT-mTOR signaling components in the clinical outcome and prognosis of human astrocytomas. Current therapeutic targeting of astrocytomas with AKT-mTOR inhibitors in preclinical and clinical stage is also discussed, including future perspectives regarding the management of these devastating tumors.
Neurology research international. 01/2012; 2012:454957.
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Sotirios G. Papageorgiou,
Panayiotis Diamantopoulos,
Georgia Levidou,
Maria K. Angelopoulou,
Panagiota Economopoulou,
Anna Efthimiou,
Nikos Constantinou,
Andreas Katsigiannis, Penelope Korkolopoulou,
Vassiliki Pappa, [......],
Marie-Christine Kyrtsonis,
Ioannis Kotsianidis,
Christina Kalpadakis,
Meletios-Athanassios Dimopoulos,
Photis Beris,
John Meletis,
Gerassimos A. Pangalis,
John Dervenoulas,
Panayiotis Panayiotidis,
Theodoros P. Vassilakopoulos
[show abstract]
[hide abstract]
ABSTRACT: Central nervous system (CNS) involvement in patients with primary mediastinal large B-cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R-CHOP ± RT in comparison to patients treated with CHOP ± RT (n = 45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R-CHOP treated patients and a 2-year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2-year actuarial incidence of 7.5% (p = 0.29). Again, both patients had isolated CNS relapses. Parenchymal-only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age-adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R-CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high-dose therapy and autologous stem cell transplantation: They are both alive and disease-free 18 and 23 months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long-term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL.
Hematological Oncology 01/2012; · 2.47 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Aberrant DNA methylation is responsible for the epigenetic silencing of genes associated with tumourigenesis and progression of cancer. In this study, we assessed the methylation status of eight genes in 49 snap-frozen primary breast tumours. Epigenetic alterations of 8 genes were analysed with methylation-specific polymerase chain reaction (MS-PCR) (DCR1, DAPK1, RASSF1A and DCR2) or methylation-sensitive high-resolution melting analysis (MS-HRM) (APC, MGMT, GSTP1 and PTEN). MS-HRM performance was validated by bisulfite pyrosequencing regarding the methylation levels of MGMT. Promoter methylation was observed in APC 54.34%, 40.4% DCR1, 37.5% DAPK1, 33.3% RASSF1A, 22.44% MGMT, 16.6% GSTP1, 6% PTEN and 0% DCR2 promoters, respectively. Interestingly, 37 out of 49 cases (75.5%) displayed aberrant promoter methylation in at least one gene. An association of MGMT promoter methylation with age and tumour grade was recorded. Moreover, a correlation with advanced T-category was elicited for GSTP1, RASSF1 and DAPK1 promoter methylation. Finally, concurrent methylation of several genes showed a marginal statistical relationship with N-category. We conclude that APC, DCR1, DAPK1 and RASSF1A promoter methylation represents a common event in breast cancer tumourigenesis. Our results suggest that GSTP1, RASSF1, DAPK1 and MGMT may be implicated in the acquisition of a more aggressive phenotype in breast cancer.
Oncology Reports 12/2011; 27(5):1630-8. · 1.84 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Lennert's lymphoma is a rare variant of peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS). The aim of this study was to further characterize this tumour.
Historical material of 97 lymphomas with a high content of epithelioid cells, collected at the Kiel Lymph Node Registry were reviewed, by applying immunohistochemistry and current diagnostic criteria. Among all cases revised, various B-cell lymphoma entities (25 cases), Hodgkin lymphomas (21 cases) and PTCL subtypes (48 cases) could be identified. A distinctive subgroup of eight PTCLs was found that were regarded as genuine Lennert's lymphomas. These cases were characterized by mild atypia, a non-activated cytotoxic phenotype [TIA1 cytotoxic granule-associated RNA binding protein (TIA1)-positive(+) and granzyme B-negative], and a substantial lack of follicular T-helper (T(FH) ) cell markers. Among the other PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL NOS, many cases with positivity for more than three T(FH) cell-associated molecules were recorded.
Our study shows that, according to current criteria, Lennert's lymphoma is a rare but distinctive entity among epithelioid cell-rich lymphomas, differing on grounds of morphology and immunophenotype from other PTCL subtypes. An additional finding is the broad morphological spectrum of epithelioid-cell rich PTCLs showing a T(FH) cell phenotype.
Histopathology 12/2011; 59(6):1173-82. · 3.08 Impact Factor
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Claudio Agostinelli,
Sylvia Hartmann,
Wolfram Klapper, Penelope Korkolopoulou,
Simona Righi,
Teresa Marafioti,
Pier Paolo Piccaluga,
Efstratios Patsouris,
Martin-Leo Hansmann,
Karl Lennert,
Stefano A Pileri
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ABSTRACT: To revise 25 cases selected from Karl Lennert's personal archive (21) and Bologna and Frankfurt Registries (four) because of cytological similarities.
All cases were provided with paraffin blocks and studied by immunohistochemistry and molecular techniques. While phenotyping was very informative, among molecular studies only EBER in situ-hybridization (ISH) was successful. Twenty-two cases were concluded as peripheral T cell lymphomas (PTCL). Of these, six were reclassified as angioimmunoblastic T cell lymphoma (AITL), 13 as PTCL, not otherwise specified (NOS), including four follicular variants and one tumour with T-zone pattern, and three as borderline tumours between AITL and PTCL/NOS. All these cases consisted homogeneously of small/medium-sized elements with mild nuclear atypia and an evident rim of clear/pale cytoplasm. On immunohistochemistry, they regularly expressed three to six follicular helper T cell (FTH)-associated markers. EBER-ISH revealed scattered EBV-infected B cells in all tumours except those with 'follicular' growth pattern. The content of follicular dendritic cells and high-endothelial venules varied significantly depending on the histotype.
This study shows that: (i) historical material can be still employed usefully, and (ii) the FTH-phenotype corresponds to a broad spectrum of PTCLs that might form a new category to be validated in future molecular and clinicopathological analyses.
Histopathology 10/2011; 59(4):679-91. · 3.08 Impact Factor
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Andreas Marnerides,
Theodoros P Vassilakopoulos,
Evmorfia Boltetsou,
Georgia Levidou,
Maria K Angelopoulou,
Irene Thymara,
Marie-Christine Kyrtsonis,
Vassiliki Pappi,
Olga Tsopra,
Panayiotis Panayiotidis,
Gerassimos A Pangalis,
Photis Beris,
Efstratios Patsouris, Penelope Korkolopoulou
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ABSTRACT: Increased proliferation rate may be associated with inferior outcome in patients with Hodgkin lymphoma (HL). Minichromosome maintenance proteins (MCMs) and D-type cyclins are essential for DNA replication.
Lymph node sections from 138 HL patients were immunohistochemically stained for cyclin D3 (CCND3), MCM2 and MCM7 aiming to investigate clinical outcome.
Higher MCM2 expression was observed in patients in early stage disease and normal albumin levels; higher MCM7 was found for asymptomatic patients, early stage disease, <5 involved sites, no anemia and normal albumin levels; higher CCND3 expression was found for older patients and normal lactate dehydrogenase (LDH). Univariate analysis revealed no correlation with failure-free (FFS) or overall survival (OS). Multivariate analysis revealed that high MCM7 expression was an adverse prognostic factor for OS, along with older age and advanced stage, while it was of borderline significance for FFS when adjusted for stage.
These results suggest that MCM7 deserves further evaluation as a potential independent prognostic factor in larger patient series.
Anticancer research 10/2011; 31(10):3585-94. · 1.73 Impact Factor
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Periklis G Foukas,
Maria Kefala,
Sotirios Papageorgiou,
Panagiotis Tsirigotis,
Panayiotis Panayiotidis, Penelope Korkolopoulou,
Aris Spathis,
John Dervenoulas,
Efstratios Patsouris,
Petros Karakitsos,
Ioannis G Panayiotides
Leukemia & lymphoma 09/2011; 53(2):345-7. · 2.40 Impact Factor
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Christina Piperi,
Vassilis Samaras,
Georgia Levidou,
Nikolaos Kavantzas,
Efstathios Boviatsis,
Kalliopi Petraki,
Athanasios Grivas,
Calypso Barbatis,
Vassilis Varsos,
Efstratios Patsouris, Penelope Korkolopoulou
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ABSTRACT: Malignant astrocytomas are highly vascular neoplasms characterized by a potent angiogenic and immunosuppressive phenotype. Th2-cytokines (IL-6/IL-8) are implicated as major regulators of glioma cell growth and invasiveness. STAT-3, a downstream transducer of cytokine signaling is positively associated with tumor angiogenesis. The present study aimed to investigate the expression of IL-8 and p-STAT-3 in 97 diffusely infiltrating astrocytomas of various grades, in relation to IL-6, VEGF, clinicopathological features, microvascular characteristics and patients' survival. IL-8 expression was localized in neoplastic cells, being associated with p-STAT-3 (p = 0.0013), IL-6 (p = 0.0004) and VEGF (p < 0.0001) around areas of necrosis as well as in perivascular inflammatory and endothelial cells. All the molecules under study correlated with tumor grade and degree of necrosis (p < 0.05, respectively). p-STAT-3, IL-8 and VEGF expression was positively associated with microvessel density (p = 0.0491, p < 0.0001 and p = 0.0118, respectively). Univariate analysis indicated that overexpression of IL-8 and IL-6 adversely affected survival in the entire cohort whereas increased p-STAT-3 expression was predictive of improved survival in high grade (III/IV) astrocytomas (p = 0.0032). In multivariate analysis only IL-8 expression (p = 0.043) retained its significance. The prognostic significance of IL-8 expression and its correlation with p-STAT-3 and VEGF implicates this novel signaling pathway in astroglial tumors progression providing new targets for effective immunotherapy.
Cytokine 06/2011; 55(3):387-95. · 3.02 Impact Factor
