Minimal change disease constitutes a major cause of nephrotic syndrome. It is regarded as a non-immune-complex mediated primary glomerulopathy and pathogenetically is characterised by podocyte injury and effacement of foot processes; therefore, it is also classified as a type of podocytopathy. T cell dysfunction with increased levels of a soluble glomerular permeability factor has been proposed to play a major role in the pathogenesis of minimal change disease. It has been therefore suggested that a dysfunction of regulatory T cells, the orchestrators of immune homeostasis, could be implicated in perpetuating T cell activation in this condition. However, the actual contribution of regulatory T cell dysfunction in the immunopathogenesis of primary minimal change disease is still largely unclear. We here propose a theoretical model based on the available evidence.
Zoledronic acid (ZA), a bisphosphonate used to prevent skeletal fractures in patients with cancers, was demonstrated to induce apoptosis in a number of cancer cells. Our previous study showed that ZA also induces autophagic cell death in metastatic prostate cancer cells. However, the clinical trials using ZA in the treatment of metastatic prostate cancer did not have a longer diseases-free period. Since most of ZA was attracted to the bone after administration, we hypothesized that local prostate cancer cells may evolve prosurvival pathways upon low concentration of ZA treatment. In this study, we investigated the inflammatory effects of ZA on osteolytic PC3 prostate cancer cell, since inflammation was reported to be related to cancer development and survival. Exposure of PC3 cells to various concentrations of ZA resulted in induction of apoptosis and autophagy. The expression of inflammatory biomarkers including interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), and NF- κ B was remarkably upregulated in response to ZA treatment in a dose- and time-dependent manner. The production of IL-6 was elevated upon ZA treatment. The antiapoptotic protein Bcl2 was increased with parallel increased level of IL-6. Our data suggest that treatment with low concentrations of ZA enhances the inflammatory profile and may serve as a prosurvival signaling pathway in PC3 cells.
Background. This study aimed to determine the prevalence and correlates of Se deficiency in patients referred for parenteral nutrition (PN) and to assess the response to a standard supplementation regimen. Methods. Adult patients (53) were recruited prior to commencing a PN regimen delivering 32 µg (0.4 µmol) Se per 24–36 h. Serum Se concentrations were measured before and daily during PN. Results. At baseline 49 (92%) patients had serum Se concentrations below the reference range (0.9–1.65 μmol/L). Se concentrations climbed during PN from 0.49±0.23 (mean ± SD) to 0.57±0.22 μmol/L (P<0.05), but in 48 (91%) patients the concentrations remained low at post-PN. Taking a Se concentration below 0.6 μmol/L as indicative of depletion in the presence of an acute phase response (APR), 37 (70%) patients had Se depletion at baseline and in 27 (51%), levels remained low at post-PN. Baseline serum Se predicted the length of hospital stay (r=-0.36, P<0.05). Increased “malnutrition universal screening tool” score predicted low Se (r=-0.93, P<0.05). Conclusions. Patients referred for PN have a high prevalence of Se deficiency, even when the APR is taken into account. Se supplementation of 32 µg Se per 24–36 h is insufficient for most patients. Baseline serum Se may have prognostic value.
In the last years, MR and CT techniques have been optimized for small bowel imaging and are playing an increasing role in the evaluation of small bowel disorders. In comparison to traditional barium fluoroscopic examinations, spatial and temporal resolution is now much more improved partially thanks to modern bowel distending agents. However, there is a global interest in implementing techniques that either reduce or eliminate radiation exposure. This is especially important in patients with chronic diseases such as inflammatory bowel disease who may require multiple studies over a lifetime. Owing to the excellent soft tissue contrast, direct multiplanar imaging capabilities, new ultrafast breath-holding pulse sequences, lack of ionizing radiation, and availability of a variety of oral contrast agents, MR is well suited to play a critical role in the imaging of small bowel disorders.
Background . Recently, gene expression profiling and its surrogate immunohistochemistry (IHC) markers classified breast cancer into four distinct molecular subtypes, which have different prognoses, targeted therapies, and/or clinical outcomes. Objective . To conduct a preliminary study, to correlate the clinical pathological profiles and taxonomy of molecular subtypes of breast cancer in Eritrea, in the Horn of Africa. Design . Review of pathology reports from Jan. 1 to Nov. 30, 2009, provided 22 cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Cytokeratin 5/6). Result . Twenty patients were female and most of them (68%) were under 50 years at presentation. 90% were invasive invasive carcinoma of no special type and were histological grade 3. The molecular subtypes were luminal A (55%), luminal B (5%), HER2 (5%), basal-like (10%), and unclassified (25%). Triple negative carcinoma (basal-like and unclassified combined) was 35%, mostly (71%) in women under 50 years with grade 3 tumours. Conclusion . Breast carcinoma in Eritrean women presents at a younger age and with a high histologic grade. The two predominant molecular subtypes are luminal A and triple negative. Determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Eritrean women with breast cancer.
The objective of current study is to evaluate the role of HPV-16 in the pathogenesis of oral epithelial dysplasias (OED) and oral squamous cell carcinoma (OSCC) by immunohistochemistry (IHC) and to know whether HPV-16 participates in disruption of the regulation of p16 INK4A suppressor protein in OED and OSCC by IHC. Histopathologically diagnosed 20 cases of OED and 20 cases of OSCC were selected from amongst the patients attending the OPD of Vasantdada Patil Dental College and Hospital, Sangli. Biopsy tissue section were then tested for HPV-16 by IHC. HPV-16 positive tissue sections were then again tested by p16 by IHC. Overall 22.5% of cases in our study were found to be positive for HPV 16 which includes 10% of cases of OED and 35% cases of OSCC. Amongst the HPV 16 positive cases, more than 60% of cells were positive for p16INK4A IHC in OED (50%) and OSCC (85.71%). Thus, HPV 16 participates in disruption of the regulation of p16INK4A suppressor protein and can be used as surrogate biomarker for detection of HPV infection in OED and OSCC.
The diagnosis of a glandular odontogenic cyst (GOC) on an incisional biopsy continues to remain a diagnostic challenge for the histopathologist. A marker for distinguishing GOC from odontogenic cysts with mucous metaplasia is thus needed in routine pathology practice. This study aimed to determine the histochemical composition of the mucous cells in the GOC and to compare the findings with the mucous cells in odontogenic cysts that show overlapping histomorphological features with the GOC. GOCs (), dentigerous cysts (DCs) (), and radicular cysts (RCs) () with mucous metaplasia were stained using the combined alcian blue(pH 2.5)-PAS histochemical technique. The cysts were evaluated for the frequencies of acidic- (type I), neutral- (type II) and mixed- (acidic and neutral (type III)) mucin containing cells. Significant differences were found between the levels of type I, type II, and type III mucous cells within the 3 cyst types, GOC (), DC (), and RC (), which all showed a predominance of type III mucous cells. There were, however, no significant differences for each mucous cell type between the 3 cyst types. GOC thus appears to share the same histochemical mucin phenotype with the mucous cells in DC and RC.
Oral submucous fibrosis (OSF) is a high risk precancerous condition characterized by changes in the connective tissue fibers of lamina propria and deeper parts of mucosa. Mast cells are local residents of connective tissue and have been identified to participate in fibrotic process. These cells produce pharmacologically active substances necessary for the physiological function of our body in response to various stimuli as and when required and also play a significant role in the pathogenesis of oral diseases. Ten healthy volunteers and 30 clinically diagnosed OSF cases with histopathological confirmation were included in the study. Immunohistochemical (c-kit) as well as acidified toluidine blue staining techniques were used to evaluate density and expression of mast cells. The mast cell density assessed using c-kit and toluidine blue showed significant difference in various stages of OSF. In general the mean number of mast cells obtained using c-kit was found to be more than that obtained using toluidine blue in various stages of OSF. The comparison of mast cell densities using immunohistochemistry (c-kit) and toluidine blue stain confirmed that c-kit is a more reliable technique to assess mast cell density in OSF.
Objectives. The aim of this study was to assess frequency of lung epithelial atypia among Shisha users.Methods. Sputum samples were collected from 200 subjects (100 Shisha users (cases) and 100 nontobacco users (controls)). Cytological smears were prepared and demonstrated using Papanicolaou and silver nucleolar organizer region (AgNORs) methods.Results. Cytological atypia was identified among 2/100 (2%) of the cases, and no cytological atypia was found among controls. Respiratory squamous metaplasia was significantly higher among cases 42/100 (42%), compared to controls 7/100 (7%) (P<0.001). Shisha users were found more susceptible for bacterial infections 34 (34%) compared to controls 3/100 (3%), (P<0.0001). The mean AgNOR dots count was higher among cases (2.3±.23) than among controls (1±.2),P<0.001.Conclusion. In view of these findings, the consumption of Shisha is a risk factor for cellular proliferation activity in respiratory epithelium. The mean AgNORs count is a useful indicator for prediction of the risk of exposure to certain carcinogenic elements that may induce lung cancer.
Objective and Aims . In the last two decades, fine-needle aspiration cytology (FNAC) of thyroid has been introduced as the most reliable and cost-effective method for diagnosing of clinically important thyroid disorders. The aim of our study was to determine the accuracy and reliability of FNAC in our center. Materials and Methods . Thyroid fine-needle aspiration cytology (FNAC) of 1639 patients from October 2007 to September 2011 was evaluated in our center. Only patients which had a solitary or multiple thyroid nodules were selected for FNA. The FNAC results are classified as benign, malignant, suspicious, and unsatisfactory. From above patients, 192 (11.7%) cases underwent surgery, and histopathologic examination was performed. By comparing the FNAC reports with the corresponding histopathologic results, the accuracy of thyroid FNAC was determined. Results . According to FNAC diagnostic criteria, there were 1054 (64.3%) benign cases, 128 (7.8%) malignant, 306 (18.66%) suspicious and 151 (9.2%) inadequate for diagnosis. In 192 cases, which underwent surgery, FNAC reports were compared with histopathologic results and statistical indices were calculated. The sensitivity, specificity, and accuracy were 91.6%, 100%, and 97%, respectively. These findings strongly support that FNAC as a useful technic for preoperative diagnosis of thyroid lesions. Conclusion . This technique is easy to perform, cost effective, minimally invasive with few complications. FNAC has high sensitivity in diagnosis of thyroid malignancy and also has high diagnostic accuracy in the evaluation of thyroid disorders.
Ki-67 labeling index has been linked to patient outcome in breast cancer patients. However, very few published reports have examined Ki-67 labeling index in African breast cancer patients. Sixty-two Sudanese breast cancer patients with primary invasive tumors were immunostained for Ki-67, ER, PR, Her-2/neu, CK5/6, and CK17. Ki-67 labeling index ranged from 0% to 50%, with a median of 5% (interquartile range 0–10). Low Ki-67 labeling index (immunostaining < 10%) was detected in 43/62 (69.4%) with a median of 0 (interquartile range 0–5), whereas high Ki-67 labeling index (immunostaining ≥ 10%) was revealed in 19/62 (30.6%) with a median of 20 (interquartile range 12–26). Ki-67 labeling index was significantly associated with tumor grade (P=0.022, Mann-Whitney U Test). There were no significant group differences between Ki-67 labeling index and ER (P=0.43), PR (P=0.7), Her-2/neu (P=0.45), CK5/6 (P=0.29), CK17 (P=0.55), pathologic stage (P=0.4), tumor histology (P=0.99), breast cancer subtypes (P=0.47), tumor size (P=0.16), and age at diagnosis (P=0.6). These results suggested that Ki-67 labeling index correlates with tumor differentiation and not with the tumor size or any other tested marker in Sudanese breast cancers. Thus, Ki-67 labeling index could be considered as a reliable measure of tumor proliferative fraction in Sudan.
We investigate the distribution of bladder tumor category and stage in Northern New England by geographic region, smoking status and over time. 1091 incident bladder cancer cases from the New England Bladder Cancer Study (NEBCS), a large population-based case-control study carried out in Maine, New Hampshire and Vermont (2001-2004), and 680 bladder cancer cases from previous case-control studies in New Hampshire (1994-2000) were used in the analysis. Of 1091 incident bladder cancer cases from the NEBCS, 26.7% of tumors were papillary urothelial neoplasms of low malignant potential (PUNLMP), 26.8% low-grade papillary urothelial carcinomas (PUC-LG), 31.3% high-grade papillary urothelial carcinomas (PUC-HG), 9.1% non-papillary urothelial carcinomas (non-PUC), and 4.3% carcinoma in situ (CIS). Approximately 70% of cases were non-invasive (Tis/Ta), and all PUNLMP cases were of the Ta category. By contrast, half of all PUC-HG carcinomas were invasive. Short-term time trend analysis within the NEBCS (2001-2004) indicated an increase in the percentage of PUNLMP (p-trend<0.0001) paralleled by a decrease in PUC-LG (p-trend=0.02), and for PUC-LG an increase in the percentage of non-invasive tumors (p-trend 0.04). Our findings suggest possible short-term trends with an increase in the percentage of PUNLMP and a change in the percentage of PUC-LG towards non-invasive disease.
Light chain proximal tubulopathy (LCPT) is an uncommon form of renal disease associated with dysproteinemias. It is characterized by intracytoplasmic deposition of crystallized mostly kappa monoclonal light chains in proximal tubules (PTs). Crystals are located within lysosomes by electron microscopy (EM). Rare lambda LCPT cases without crystals by EM were described. Retrospectively, we reviewed clinical, light microscopic (LM), immunofluorescence (IF), and EM findings in 9 cases) (8 males, 1 female; mean age 57 years (38–81)) with multiple myeloma. LM showed abundant cytoplasmic droplets in PT cells in all cases. Droplets were also present in the podocytes, endothelial and parietal cells in one case. IF revealed staining of crystals with kappa in 3 and lambda in 6. EM showed electron dense rectangular, rhomboid, or needle shaped crystals in PT cells in 3 cases (33%), one of which had crystals in podocytes and interstitial cells. Six lambda LCPT cases showed no crystals by EM (67%). This may reflect differences in the physicochemical properties of light chains. The mechanisms of crystal accumulation in these cells and the significance of this finding are unknown.
Background . The standard of care for patients with operable gastric and gastro-oesophageal junction (GOJ) tumours involves neoadjuvant chemotherapy. This improves survival and reduces risk of tumour recurrence following surgery. The various grading criteria published to assess histological response to neoadjuvant treatments have never been compared in terms of their reproducibility and ability to predict survival. Methods . A study was carried out of 66 patients with gastric and GOJ (types II and III) adenocarcinoma treated with neoadjuvant chemotherapy according to the MAGIC protocol. Histology slides were reviewed independently by two histopathologists using three published grading systems (Mandard, Japanese, and Becker). Histological, demographic, and survival data were collected. The kappa statistic was used to assess interobserver reproducibility. Results . Three (5%) patients had a complete pathological response. There was reasonable interobserver agreement for the grading systems: κ -scores = 0.44 (Mandard), 0.28 (Japanese), and 0.51 (Becker). Only Mandard and Becker scores provided prognostic information: 5-year overall survival rates of 100% for complete or near complete responders versus 35% for nonresponders () for both. Positive lymph nodes () and resection margins () were associated with poor survival. Conclusion . Becker’s score is most reproducible for the evaluation of histological response. Furthermore, lymph node and resection margins status provides prognostic information.
Cancer cells display changes that aid them to escape from cell death, sustain their proliferative powers, and shift their metabolism toward glycolytic energy production. Mitochondria are key organelles in many metabolic and biosynthetic pathways, and the adaptation of mitochondrial function has been recognized as crucial to the changes that occur in cancer cells. This paper zooms in on the pathologic evaluation of mitochondrial markers for diagnosing and staging of human cancer and determining the patients’ prognoses.
Objective . To evaluate the serum and tissue levels and local expression pattern of tenascin, a high molecular weight extracellular matrix protein, in eutopic and ectopic endometrium from patients with and without endometriosis and to compare the proliferative and secretory phase differences. Materials and Methods . Thirty women with endometriosis and fifteen women without endometriosis undergoing surgery for benign indications were included in the study. Serum and tissue levels and proliferative and secretory phase expression patterns of tenascin in the ectopic and eutopic endometrium were analyzed with immunohistochemistry and immunoassays. The results were compared with Mann-Whitney U test. P values <0.05 were considered as statistically significant. Results . Tenascin expression was detected in both of eutopic and ectopic endometrium of women with and without endometriosis. In immunohistochemical staining, intense staining of tenascin was observed in glandular cells of eutopic and ectopic endometrial tissue samples of both groups during secretory phase (P<0.01). Eutopic and ectopic tissue levels of tenascin were higher than serum tenascin levels only secretory phase (P=0.02). There was no significant difference between groups for tissue and serum levels of tenascin during cycle phases. Conclusion . Tenascin expression showed cyclic change on eutopic and ectopic endometrium.
Introduction . Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting the human population. Tumor pathogenesis implies a multistep process in which cells acquire features that enable them to become tumorigenic and ultimately malignant. The process of OSCC carcinogenesis can be reproduced in animal models, the OSCC induction with 4-nitroquinoline-1-oxide (4NQO) in mice is a widely used tool for studying tumor pathogenesis. Objective . The aim of the present study was to determine the progressive changes in basal lamina and connective tissue remodeling during 4NQO-induced OSCC carcinogenesis. Material and Methods . Samples were classified according to “International Histological Classification of tumors” in mild, moderate, and severe dysplasia and invasive carcinoma. Five samples of each pathologic entity and control healthy tongues were used. Immunohistochemical analysis of collagen IV as well as histochemical analysis of glycosylated molecules (PAS) and collagen I (Picro Sirius red) were performed. Results . During experimental-induced carcinogenesis by 4NQO a progressive basal lamina destruction and collagen I disorganization in adjacent connective tissue can be observed. Conclusion . Our results confirm previous studies that show alterations in extracellular matrix (ECM) in malignant lesions, validating the experimental carcinogenesis induced by 4NQO.
Confocal laser endomicroscopy (CLE) is a novel tool in the endoscopist’s armamentarium. It allows on-site histological information. The ability of gastroenterologists to interpret such microscopic information has been demonstrated in multiple studies from the upper and lower gastrointestinal tract. Recently, the field of application has expanded to provide hepatobiliary and intra-abdominal CLE imaging. CLE allows “smart,” targeted biopsies and is able to guide endoscopic interventions. But CLE is also translational in its approach and permits functional imaging that significantly impacts on our understanding of gastrointestinal diseases. Molecular imaging with CLE allows detection and characterization of lesions and may even be used for prediction of response to targeted therapy. This paper provides a comprehensive review over current applications of CLE in clinical applications and translational science.
Increased expression of cyclin A2 protein has been detected in different types of cancers. However, its prognostic importance appears to differ between tumours. The significance and precise mechanisms behind cyclin A2 overexpression remain to be elucidated. We used real-time PCR to examine CCNA2 amplification in tumour cells isolated by laser microdissection and in total tumour tissue in colon cancer patients in which overexpression of cyclin A2 protein had been revealed by immunohistochemistry (n=22 patients). The results were verified by FISH. CCNA2 amplification was not detected in either the isolated tumour cells or the total tumour tissue. We verified our methods by demonstrating amplification of CCNA2 by real-time PCR in three out of eight breast tumours that overexpressed cyclin A2 protein (this frequency is consistent with the findings of others). However, FISH did not reveal any CCNA2 amplification in the breast tumours, but it did reveal polysomy of chromosome 4 or segments of chromosome 4 in three tumour tissue samples, indicating the importance of verifying the real-time PCR results with another method. To conclude, the increased cyclin A2 protein expression in these patients could not be explained by CCNA2 amplification in isolated colonic tumour cells.
Overexpression of the Snail gene transcriptional repressor promotes an epithelial-to-mesenchymal transition (EMT) in epithelial tumor cell lines. In this study, we aimed to determine the correlation between Snail protein expression and clinicopathological features and to test whether Snail can be used as a marker to distinguish gastric carcinomas from benign tissues in biopsy samples. The results of immunohistochemistry with an antibody against Snail showed that most adenocarcinomas had positive Snail expression, whereas weak Snail expression was detected in a small number of gastritis and gastric adenomas. Snail-positive cells were detected in the stroma as well as in the glandular epithelium in some adenocarcinomas. In addition to Snail immunostaining, immunostaining of the EMT-related molecules, E-cadherin and vimentin, was performed. E-cadherin was not detected in adenocarcinomas that expressed Snail, whereas gastritis and adenomas stained positively for E-cadherin. Vimentin expression was seen in adenocarcinomas with positive Snail expression, whereas gastritis and adenomas did not express vimentin. In conclusion, we propose that Snail is a useful biomarker to distinguish gastric adenocarcinomas from benign lesions in biopsy samples.
