Transcription factors encoded by Homeobox (HOX) genes play numerous key functions during early embryonic development and differentiation. Multiple reports have shown that mis-regulation of HOX gene expression plays key roles in the development of cancers. Their expression levels in cancers tend to differ based on tissue and tumor type. Here, we performed a comprehensive analysis comparing HOX gene expression in different cancer types, obtained from The Cancer Genome Atlas (TCGA), with matched healthy tissues, obtained from Genotype-Tissue Expression (GTEx). We identified and quantified differential expression patterns that confirmed previously identified expression changes and highlighted new differential expression signatures. We discovered differential expression patterns that are in line with patient survival data. This comprehensive and quantitative analysis provides a global picture of HOX genes' differential expression patterns in different cancer types.

BACKGROUND AND OBJECTIVE Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions. PATIENTS AND METHODS Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997-2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002-2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m2 for >3 months and were staged according to the National Kidney Foundation guidelines. RESULTS Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy. CONCLUSIONS CKD is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

The Significance of Image Analysis for Cancer Diagnosis Jona J. Sela1 ∗, Alfred Bruckstien2, Gal Goshen3, Uri Dubin3, Nir Karasikov3, and Juri Kopolovic4 1Institute of Dental Sciences, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel 2Computer Science Department Technion, Technological Institute, Haifa 32000, Israel 3Ardia, Medical Products, Haifa 31250, Israel 4Department of Pathology, Hebrew University-Hadassah, Faculty of Medicine Jerusalem 91120, Israel

You have accessJournal of UrologyProstate Cancer: Detection and Screening1 Apr 2011989 A NOVEL METHOD FOR REAL-TIME PROSTATE TISSUE CHARACTERIZATION Zohar Dotan, Eddie Fridman, Arie Lindner, Jacob Ramon, Dov Pode, Jacob Bejar, Juri Kopolovic, Galina Pizov, Judith Sandbank, Ran Katz, Amos Shapiro, Yaniv Shilo, and Ofer Nativ Zohar DotanZohar Dotan Ramat Gan, Israel More articles by this author , Eddie FridmanEddie Fridman Ramat Gan, Israel More articles by this author , Arie LindnerArie Lindner Zrifin, Israel More articles by this author , Jacob RamonJacob Ramon Ramat Gan, Israel More articles by this author , Dov PodeDov Pode Jerusalem, Israel More articles by this author , Jacob BejarJacob Bejar Haifa, Israel More articles by this author , Juri KopolovicJuri Kopolovic Haifa, Israel More articles by this author , Galina PizovGalina Pizov Jerusalem, Israel More articles by this author , Judith SandbankJudith Sandbank Zrifin, Israel More articles by this author , Ran KatzRan Katz Jerusalem, Israel More articles by this author , Amos ShapiroAmos Shapiro Jerusalem, Israel More articles by this author , Yaniv ShiloYaniv Shilo Zrifin, Israel More articles by this author , and Ofer NativOfer Nativ Haifa, Israel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1021AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The aim of radical prostatectomy (RP) is completely removing the prostate gland with negative surgical margins. The presence of cancer at the surgical margin is associated with higher probability of disease progression. Current methods of intra-operative margin assessment are inaccurate or time-consuming. The study goal was to evaluate the ability of a novel device (Dune Medical Devices) in differentiating between cancer and benign prostatic tissue. METHODS Between November 2007 and May 2008, 49 patients undergoing RP were enrolled in this study in 4 medical centers. The device was applied to numerous intra- and extra-capsular sites of freshly excised RP specimens. Measurement sites were accurately marked and analyzed histologically. The ability of the device to differentiate between malignant and non-malignant sites was assessed. RESULTS A total of 15,156 measurements from 45 patients were analyzed. Differentiation of the intra-capsular malignant sites from extra-capsular non-malignant sites (bladder neck and apex regions), depends on the cancer feature size. The differentiation was achieved with sensitivity and specificity of 93.6 (95% CI: 88–98) and 94.1 (95% CI: 93–95) respectively, at feature sizes at or above 0.8mm in diameter. The device ability to discriminate between all intra-capsular malignant and non-malignant measurement sites in terms of sensitivity and specificity are 80.8 (95% CI: 73–87) and 68.4 (95% CI: 67–69), respectively. CONCLUSIONS Radio-Frequency near-field spectroscopy sensor can differentiate efficaciously between cancer and benign prostate tissue. The sensor's dimensions and design should enable use in open, laparoscopic, and robotic RP in order to evaluate the surgical margins intraoperatively. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e399 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Zohar Dotan Ramat Gan, Israel More articles by this author Eddie Fridman Ramat Gan, Israel More articles by this author Arie Lindner Zrifin, Israel More articles by this author Jacob Ramon Ramat Gan, Israel More articles by this author Dov Pode Jerusalem, Israel More articles by this author Jacob Bejar Haifa, Israel More articles by this author Juri Kopolovic Haifa, Israel More articles by this author Galina Pizov Jerusalem, Israel More articles by this author Judith Sandbank Zrifin, Israel More articles by this author Ran Katz Jerusalem, Israel More articles by this author Amos Shapiro Jerusalem, Israel More articles by this author Yaniv Shilo Zrifin, Israel More articles by this author Ofer Nativ Haifa, Israel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

OBJECTIVES:HER2/neu (HER2) overexpression occurs in approximately 20% of breast cancers and is associated with aggressive disease. Although a significant number of HER2-positive tumors also express hormone receptors (HR), the effects HR expression has on clinical characteristics, including response to trastuzumab among HER2-positive breast cancer, has not been elucidated yet.METHODS:A retrospective analysis of consecutive metastatic HER2-positive breast cancer patients was conducted in 2 medical centers. Associations between hormone receptors expression and clinical variables, and metastatic spread pattern and survival were studied.RESULTS:The study population included 137 metastatic HER2-positive breast cancer patients, 56 of them were HR-positive and 81 were HR-negative. No significant differences between the 2 groups were found for demographic and clinical characteristics, including age, stage at diagnosis, tumor histology, and grade. Similar response rate to trastuzumab was observed in both study groups. Significantly, longer, median, disease-free, and overall survival was noted among the HR-positive patients. Patients in the HR-negative group had significantly more liver metastases, a trend for more brain metastases, and less bone metastases. There was a strong trend for more visceral metastases in the HR-negative group.CONCLUSIONS:Our results suggest an important role for HR expression in modulating metastases predilection and disease progression in HER2-positive breast cancer.

The objective of this study was to compare the expression of the nerve growth factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced-stage (FIGO stage III-IV) carcinomas, and to assess a possible association between NGF receptor expression and mitogen-activated protein kinase (MAPK) activation in borderline tumors and FIGO stage I carcinomas. Sections from 119 borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced-stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I carcinomas and borderline tumors using phospho-specific antibodies against the extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage carcinomas compared with both borderline and stage I carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor expression showed no association with MAPK activation in borderline and stage I carcinomas. In conclusion, expression of biologically active p-TrkA receptor at the cell membrane is up-regulated along tumor progression in ovarian carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors probably signal via MAPK-independent pathways in ovarian carcinoma.

Many studies have been performed on chromosomal aberrations of extranodal marginal zone lymphomas. However, only a few have been published so far on ocular adnexal marginal zone lymphomas. We studied 18 cases of orbital lymphoid cell infiltrates. Using fluorescence in situ hybridization (FISH), we studied some of the most common chromosomal aberrations found in extranodal marginal zone lymphomas as: trisomies 3, and rearrangements of the 18q21 MALTI gene to detect the translocations t(11;18)(q21;q21) and t(14;18)(q32;q21)MALT1. Our goals were as follows: (1) study those aberrations in our material and compare them with the literature, (2) check their prognostic significance, and (3) check whether studying those aberrations with FISH can be used as a diagnostic tool to differentiate reactive from neoplastic infiltrates, in addition to immunohistochemistry and polymerase chain reaction. We found a high frequency of trisomies 3 (68%) and 18 (56.6%), the highest published so far in orbital lymphomas. On the other hand, no rearrangement was seen in any of our cases. The histologic picture and the clinical course were the same when there was one or more aberrations. As for the diagnostic significance, the presence of a prior, concurrent, or subsequent lymphoma in almost all the positive for aberrations cases suggests that either the orbital infiltrates in these cases are lymphomas, or they have, at least, a malignant potential or a genetic instability. Therefore, the demonstration of these numerical aberrations by FISH may be an additional sensitive, reliable, and relatively simple tool to differentiate reactive from neoplastic orbital lymphoid cell infiltrates when the immunohistochemistry and polymerase chain reaction, performed in a busy and routine-based histopathology laboratory, are unsatisfactory.

Background Potential health effects of cell phone use in children have not been adequately examined. As children are using cell phones at earlier ages, research among this group has been identified as the highest priority by both national and international organisations. The authors previously reported results from the Danish National Birth Cohort (DNBC), which looked at prenatal and postnatal exposure to cell phone use and behavioural problems at age 7 years. Exposure to cell phones prenatally, and to a lesser degree postnatally, was associated with more behavioural difficulties. The original analysis included nearly 13 000 children who reached age 7 years by November 2006. Methods To see if a larger, separate group of DNBC children would produce similar results after considering additional confounders, children of mothers who might better represent current users of cell phones were analysed. This ‘new’ dataset consisted of 28 745 children with completed Age-7 Questionnaires to December 2008. Results The highest OR for behavioural problems were for children who had both prenatal and postnatal exposure to cell phones compared with children not exposed during either time period. The adjusted effect estimate was 1.5 (95% CI 1.4 to 1.7). Conclusions The findings of the previous publication were replicated in this separate group of participants demonstrating that cell phone use was associated with behavioural problems at age 7 years in children, and this association was not limited to early users of the technology. Although weaker in the new dataset, even with further control for an extended set of potential confounders, the associations remained.

The aim of this study was to analyze the expression and clinical role of DJ-1, a negative regulator of PTEN (phosphatase and tensin homolog deleted on chromosome 10), in ovarian carcinoma, and investigate the putative association between DJ-1 levels and expression of its transcriptional regulators specificity protein 1 (Sp1) and specificity protein 3 (Sp3). Effusions (n = 72) and solid tumors (n = 57, 42 primary and 15 metastases) were analyzed for DJ-1 messenger RNA (mRNA) expression using reverse transcriptase–polymerase chain reaction. Most specimens (48 effusions, 50 solid tumors) were additionally analyzed for Sp1 and Sp3 mRNA expression. PTEN protein expression was analyzed in 201 effusions and 92 solid tumors using immunohistochemistry. DJ-1 mRNA was expressed in more than 80% of specimens, with no preferential anatomical site. DJ-1 expression was positively associated with Sp1 expression in effusions (P = .03) and with Sp1 (P = .02) and Sp3 (P = .002) expression in solid tumors. In effusions, DJ-1 expression was higher in postchemotherapy compared with prechemotherapy specimens (P = .012). Higher DJ-1 levels (P = .027) and more advanced FIGO stage (IV versus III; P = .003) correlated with shorter progression-free survival in univariate analysis for patients with postchemotherapy effusions. PTEN expression was low in effusions and solid tumors (23% and 13%, respectively), and its expression showed no association with DJ-1 levels or survival. Our data show that DJ-1 is frequently expressed in advanced-stage ovarian carcinoma at all anatomical sites and is coexpressed with its transcriptional regulators Sp1 and Sp3. In contrast, PTEN expression is infrequent in this disease. These findings may provide one of the molecular mechanisms that mediate cancer cell survival and aggressiveness in this tumor.

Objective. To analyze the expression of the AP-2-gamma transcription factor in ovarian borderline tumors, early-stage ovarian carcinoma and advanced-stage ovarian carcinoma, and to evaluate its prognostic role in advanced-stage tumors.Methods. Sections from 14 normal ovaries, 75 borderline tumors, 22 FIGO stage I invasive ovarian carcinomas, and 306 advanced-stage (FIGO stages II-IV) ovarian carcinomas (42 primary tumors, 62 solid metastases, 202 effusions) were evaluated for expression of the transcription factor AP-2 gamma using immunohistochemistry. Sixty-three effusions and two cell lines (SKOV-3 and OVCAR-3) were additionally studied using immunoblotting. The prognostic role of AP-2 gamma in advanced-stage carcinomas was analyzed.Results. AP-2 gamma was detected in the nucleus of tumor cells in 28/75 (37%) borderline tumors, 13/22 (59%) FIGO stage I carcinomas, and 255/306 (83%) advanced-stage carcinomas (P < 0.001, Chi-square test). Benign ovaries were uniformly negative. Expression was largely limited to carcinoma cells in effusions. Solid lesions and effusions from advanced-stage carcinomas showed comparable expression. Immunoblotting showed AP-2 gamma expression in 59/61 effusions and both cell lines. AP-2 gamma expression did not correlate with survival.Conclusions. AP-2 gamma expression is upregulated in advanced-stage ovarian carcinoma compared to early-stage carcinomas, borderline tumors, and the ovarian surface epithelium, and AP-2 gamma is specifically localized to cancer cells in effusions, suggesting a role in tumor progression. The lack of predictive value for this transcription factor in advanced-stage disease may be related to its frequent expression. (C) 2005 Elsevier Inc. All rights reserved.

Purpose: Cyclooxygenase-2, a key enzyme in prostaglandin biosynthesis, has been shown to be involved in the modulation of cell growth, inflammation and apoptosis. Its involvement in the development of several human neoplasms has also been documented as well as the significant antitumor effects of its inhibitors. To our knowledge cyclooxygenase-2 expression in Wilms tumor has not been studied.Materials and Methods: A tissue microarray multitissue block was prepared from 14 samples of Wilms tumor, each from a different patient, from xenografts derived thereof, and from normal human lung, liver, renal cortex and medulla tissues as controls. Each sample was represented in the block by 3 or 4 cores 0.6 mm in diameter. After serial slicing to 4 Am the histological slides were stained with hematoxylin and eosin, and immunostained with anti-cyclooxygenase-2 antibodies. Immunostaining was graded semiquantitatively according to the percent of stained cells with the cytoplasmic pattern of staining and according to staining intensity.Results: All authentic human pathological samples except I anaplastic Wilms tumor as well as Wilms tumor xenografts expressed cyclooxygenase-2 in all Wilms tumor cellular components except the stroma. Expression was also observed in Wilms tumor lung metastasis and in tumors that overgrew chemotherapy. In comparison, cyclooxygenase-2 expression in normal kidneys was less prominent than in Wilms tumor samples and it was confined to the tubular epithelium in the cortex and medulla.Conclusions: Cyclooxygenase-2 expression is characteristic of all nonanaplastic Wilms tumors at all stages. It is similar to the previously observed pan-expression of ErbB2 receptors in these tumors. The potential therapeutic role of cyclooxygenase-2 inhibitors should be evaluated for Wilms tumor.

We present a case of a 33-year-old woman who underwent excisional breast biopsy due to a left nipple mass. Histological examination revealed the morphologic and immunohistochemical pattern of syringomatous adenoma of the nipple. This is a rare lesion of the breast that can clinically mimic breast carcinoma, but harbors a benign and only locally aggressive course. Awareness of both the clinician and the pathologist for the possibility of diagnosing this tumor in the nipple region is mandatory to avoid mastectomy and lymph node dissection.

The authors present the application of wet SEM for histopathological assessment, a technology for imaging fully hydrated samples at atmospheric pressure in a scanning electron microscope (SEM). Both transmission and scanning electron microscopy techniques usually require long and complex sample preparation of the tissues. In marked contrast, a rapid preparation of tissues is described for evaluation by SEM imaging. The wet SEM technology successfully demonstrated both histological and ultrastructural features of several CNS tumors: Rosette formation and intracytoplasmic lumens were observed in ependymoma; numerous fibrillary processes in fibrillary astrocytoma; and focal rosette formation with no intracytoplasmic lumens in medulloblastoma. Application of this method simultaneously with frozen section may improve rapid intraoperative diagnosis of these intracranial tumors.

Progress in the processing of wet tissues, without the need of fixation and complex preparation procedures, may facilitate the microscopic examination of tissues and cells. Microscopic examination of tissues is a central tool in clinical diagnosis as well as in diverse areas of research. The authors present the application of Wet SEM, a technology for imaging fully hydrated samples at atmospheric pressure in a scanning electron microscope (SEM). The technique is based on 2 principles. First, samples are imaged in sealed specimen capsules and are separated from the evacuated interior of the electron microscope by a thin, electron-transparent partition membrane that is strong enough to sustain a 1-atm pressure difference. Second, imaging is done in a SEM, based on detection of backscattered electrons, which penetrate a few microns into the specimen and thus give information on the cellular level.

Introduction: Anti phospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiotipin/beta(2) glycoprotein I (beta 2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta 2GPI-related target epitope recognized by the anti-beta 2GPI Abs on the valves.Materials and methods: In order to find the beta 2GPI-retated target epitopes recognized by the anti-beta 2GPI antibodies on the valves, we used beta 2GPI-related synthetic peptides. The presence of anti-beta 2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta 2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta 2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody.Results: Among the beta 2GPI-retated synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta 2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta 2GPI anti-idiotypic Abs for binding the anti-beta 2GPI Abs on the valve by a competition assay.Conclusion: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin. (c) 2004 Elsevier Ltd. All rights reserved.

Bisphosphonates currently are important antiresorptive agents used in the treatment of metabolic bone diseases, including tumour-associated osteolysis and hypercalcaemia, Paget’s disease and osteoporosis. These drugs cause a loss of the osteoclast ruffled border, disruption of the osteoclast cytoskeleton and inhibition of actin ring formation, sufficient to prevent bone resorption [1]. Several studies have demonstrated that high concentrations of bisphosphonates can cause apoptotic cell death of mouse, rat and rabbit osteoclasts in vitro and in vivo by inhibiting the mevalonate pathway and protein prenylation [2]. Bisphosphonates are excreted unchanged via the kidneys. The high drug levels attained in the kidney may cause renal toxicity through a mechanism similar to that described in osteoclasts. Short-term [3] and long-term [4–6] tubular toxicity of pamidronate were reported in humans. Recently, an association between collapsing glomerulopathy and prolonged intravenous treatment with high-dose pamidronate was reported in patients with malignancy [4,5]. We describe a patient with multiple myeloma in remission who developed collapsing glomerulopathy without significant tubular damage after long-term treatment with standard-dose pamidronate.

Ets transcription factors play a central role in invasion and metastasis through regulation of synthesis of proteolytic enzymes and angiogenic molecules. The objective of this study was to investigate the role of PEA3 in tumor progression of ovarian and breast carcinoma metastatic to effusions, and to evaluate the expression of Ets-2 and Erg in ovarian carcinoma. Ovarian (83 malignant effusions, 102 corresponding solid lesions) and breast (33 malignant effusions, 40 corresponding solid lesions) carcinomas were evaluated for expression of PEA3 using mRNA in situ Hybridization (ISH). Expression of Ets-2 and Erg mRNA was analyzed in 50 ovarian carcinoma effusions using the same method. PEA3 mRNA expression was comparable at all sites in ovarian carcinoma (44 out of 83; 53% of effusions, 48 out of 102; 47% of solid tumors). PEA3 mRNA expression in effusions correlated with mRNA expression of the previously studied αv ( P =0.022), α6 ( P <0.001) and β1 ( P <0.001) integrin subunits, the matrix metalloproteinase (MMP) inducer EMMPRIN ( P =0.015) and interleukin-8 (IL-8) ( P =0.033). Erg and Ets-2 mRNA was expressed in 15 out of 50 (30%) and 18 out of 50 (36%) effusions, respectively, and co-localized with PEA3 ( P =0.017 for Erg, P =0.004 for Ets-2). In breast carcinoma, PEA3 expression was seen in 19/40 (48%) of solid lesions, with a significant upregulation in corresponding effusions compared to primary tumors (24 out of 33; 73%, P =0.038). PEA3 mRNA expression in effusions obtained prior to the institution of chemotherapy predicted significantly shorter overall survival in univariate analysis (24 vs 37 months, P =0.03), with a similar trend for Erg (13 vs 30 months, P =0.1). In conclusion, PEA3 is expressed at all anatomic sites in serous ovarian cancer and co-localizes with Erg, Ets-2 and several metastasis-associated molecules. PEA3 mRNA expression is a novel marker for tumor progression to malignant effusion in breast carcinoma, and predicts poor outcome in effusions sampled prior to therapeutic intervention in ovarian carcinoma. These findings support a biological role for Ets transcription factors in these malignancies and suggests that they may be targets for therapeutic intervention.

Objective To analyze the somatic pattern of p53 expression and BRCA germline mutation status in Israeli patients with both ovarian (OvCa) and breast cancer (BrCa). Methods The study group comprised 43 Israeli patients with OvCa, all of whom had previous primary BrCa. p53 immunohistochemistry (IHC) on all available archival tissues and genotyping for the three predominant Jewish germline BRCA1–2 mutations were carried out. Samples from 64 patients with solitary OvCa and 61 with solitary BrCa were similarly analyzed as controls. Results p53 expression pattern and the immunopositivity rate were similar in the ovarian and breast tumors within the study group and in the two control groups: positive p53 staining was detected in 68% of ovarian tumors in the study group compared with 71.9% in the controls, and in 19.4% of the BrCa tissues versus 21.3% in the controls. Within the study group, advanced stage OvCa had a higher rate of p53 expression (84%) compared to early stage disease (38.5%) (P = 0.006). This difference was not apparent in the solitary OvCa control group. OvCa in BRCA1–2 mutation carriers from the study group were more likely to display positive p53 staining (79%), especially in tumors diagnosed before the age of 60 (90%) compared with the OvCa of noncarriers (60%), but this difference was statistically insignificant. The p53 expression rate in BrCa samples from the study group was not associated with BRCA1–2 mutation status. Conclusions Positive p53 expression, detected by IHC, in OvCa patients with previous primary BrCa is significantly higher in advanced stage disease in BRCA1–2 mutation carriers. There is a higher positive p53 expression somatically in OvCa in BRCA1–2 carriers in whom OvCa was diagnosed before the age of 60 years, although this trend is not statistically significant. These observations suggest that somatic p53 inactivation may be an important event in ovarian tumorigenesis in this subset of patients.

Quantomix Ltd., Rehovot, Israel Progress in the processing of wet tissues, without the need of fixation and complex preparation procedures, may facilitate the microscopic examination of tissues and cells. Microscopic examination of tissues is a central tool in clinical diagnosis as well as in diverse areas of research. The authors present the application of Wet SEM, a technology for imaging fully hydrated samples at atmospheric pressure in a scanning electron microscope (SEM). The technique is based on 2 principles. First, samples are imaged in sealed specimen capsules and are separated from the evacuated interior of the electron microscope by a thin, electron-transparent partition membrane that is strong enough to sustain a 1-atm pressure difference. Second, imaging is done in a SEM, based on detection of backscattered electrons, which penetrate a few microns into the specimen and thus give information on the cellular level.

Background: Hirschsprung's disease (HD) is a congenital disorder characterised by the absence of ganglion cells in the large bowel, leading to functional obstruction and colonic dilatation proximal to the affected segment.A subclass of nerve cell bodies in both submucosa and myenteric ganglia of the human gastrointestinal tract were found to show immunopositivity for calretinin, a calcium binding protein, which plays an important role in the organisation and functioning of the central nervous system.Aim: To investigate calretinin immunostaining in ganglionic and aganglionic HD colon specimens, and compare it with staining for S100, neurone specific enolase, and c-kit.Methods: Ten large bowel, full thickness specimens from patients with classic rectosigmoid HD were selected from the pathology repository.In total, 54 paraffin wax blocks-24 from the ganglionic zone, 17 from the aganglionic zone, and 13 from the transitional zone-were processed.Results: Calretinin was not expressed in aganglionic segments of HD and associated nerve fibres, whereas in ganglionic HD segments and in normal colon both ganglion cells and nerve fibres were immunopositive.In addition, c-kit showed an altered distribution in the interstitial cells of Cajal.The transitional zone showed a broad spectrum of histomorphological and immunohistochemical patterns of both calretinin and c-kit expression. Conclusion:The absence of calretinin expression may serve as a diagnostic aid in identifying aganglionic segments in HD.