[Show abstract][Hide abstract] ABSTRACT: Breast cancer coexisting with lymphoma is a rare condition with various diagnostic and therapeutic implications. In this report, we describe the case of a 55-year-old Caucasian woman who presented with simultaneous ductal carcinoma in situ of the right breast, and follicular lymphoma involving an inguinal lymph node and the left breast. The patient underwent local excision and radiotherapy for the ductal carcinoma in situ, while a watch and wait strategy was adopted for the lymphoma. Two years later, the patient presented with multifocal ductal carcinoma of the left breast and reappearance of the lymphoma in the left axillary lymph nodes. She underwent bilateral mastectomy, left sentinel node biopsy, and chemotherapy. Synchronous follicular lymphoma and bilateral metachronous breast carcinoma has not been described previously. Diagnosis is based on tissue histology after excision or a needle biopsy. Treatment for these two diseases is distinct, and a multidisciplinary approach should be adopted.
Journal of Breast Cancer 10/2015; 18(3):296-300. DOI:10.4048/jbc.2015.18.3.296 · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. Methods: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Results: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (γGT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (pper se constitutes an aggravating factor as demonstrated by the elevated γGT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007). Conclusion: The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions.
[Show abstract][Hide abstract] ABSTRACT: Background:
Selection of NSCLC patients for targeted therapy is currently based upon the presence of sensitizing mutations in EGFR and EML4/ALK translocations. The heterogeneity of molecular alterations in lung cancer has led to the ongoing discovery of potential biomarkers and targets in order to improve survival.
This study aimed to detect alterations in EGFR, KRAS, BRAF, PIK3CA, MET-gene copy number and ALK rearrangements in a large cohort of 956 NSCLC patients of Hellenic origin using highly sensitive techniques and correlations with clinicopathological characteristics.
Mutations were detected in EGFR 10.6% (101 out of 956 samples), KRAS 26.5% (191 out of 720 samples), BRAF 2.5% (12 out of 471 samples), PIK3CA 3.8% (7 out of 184 samples), MET gene amplification was detected in 18% (31 out of 170) and ALK rearrangements in 3.7% (4 out of 107 samples). EGFR mutations were detected in exon 19 (61.4% of mutant cases), exon 21 p.Leu858Arg (19.8%), exon 20 (15.8%), exon 18 (2.9%) and were correlated with gender histology, smoking status and TTF1 staining. p.Thr790Met mutant cases (3.9%) displayed concurrent mutations in exons 19 or 21. Negative TTF-1 staining showed strong negative predictive value for the presence of EGFR mutations. KRAS mutations were associated with histology, the most common mutation being p.Gly12Cys (38%).
In conclusion, only 89 patients were eligible for EGFR -TKIs and ALK inhibitors therapy, whereas 257 patients showed other alterations, highlighting the necessity for a detailed molecular profiling potentially leading to more efficient individualized therapies for NSCLC patients.
PLoS ONE 07/2015; 10(7). DOI:10.1371/journal.pone.0133859 · 3.23 Impact Factor
[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 · 3.23 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; 30(6). DOI:10.14670/HH-30.629 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p
Clinical Chemistry and Laboratory Medicine 12/2014; 53(9). DOI:10.1515/cclm-2014-0798 · 2.71 Impact Factor
[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 11/2014; 2014:526129. DOI:10.1155/2014/526129
[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.
[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. · 1.83 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.
[Show abstract][Hide abstract] ABSTRACT: The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.
[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
[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.
[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 · 2.65 Impact Factor