BMC Clinical PathologyPub Date : 2014-10-22eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-42
Davis R Ingram, Lloye M Dillon, Dina Chelouche Lev, Alexander Lazar, Elizabeth G Demicco, Burton L Eisenberg, Todd W Miller
{"title":"Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma.","authors":"Davis R Ingram, Lloye M Dillon, Dina Chelouche Lev, Alexander Lazar, Elizabeth G Demicco, Burton L Eisenberg, Todd W Miller","doi":"10.1186/1472-6890-14-42","DOIUrl":"https://doi.org/10.1186/1472-6890-14-42","url":null,"abstract":"<p><strong>Background: </strong>Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes. Estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR) have been implicated in the pathophysiology of other cancer types. We sought to comprehensively determine temporal expression patterns of these receptors in LS.</p><p><strong>Methods: </strong>We analyzed 561 histologically subtyped LS specimens from 354 patients for expression of ER, PR, and AR by immunohistochemistry (IHC) using diagnostic-grade reagents and protocols. The fractions of positively stained tumor cells were scored within each specimen. IHC scores were compared across LS subtypes using the Kruskal-Wallis test, and subtypes were compared using Dunn's post-hoc test. Ages of patients with receptor-positive vs. -negative LS were compared by t-test. Genders and races were compared for hormone receptor positivity using Fisher's exact test and Chi-square analysis, respectively. Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p< 0.05 was considered significant.</p><p><strong>Results: </strong>ER and AR were frequently expressed in LS, while few tumors expressed PR. Most of the ER + and AR + samples were of the well-differentiated LS subtype. A smaller fraction of de-differentiated LS expressed ER or AR, but expression was common within well-differentiated regions of tumors histologically classified as de-differentiated LS. In LS specimens from patients who underwent multiple surgeries over time, receptor expression frequently changed over time, which may be attributable in part to intratumor heterogeneity, varying degrees of de-differentiation, and biopsy bias. ER and AR were frequently co-expressed. Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis. Receptor expression was not associated with altered recurrence-free survival.</p><p><strong>Conclusions: </strong>ER and AR are commonly expressed in LS, particularly in well-differentiated tumors. These data warrant further functional study to determine receptor function in LS, and the potential efficacy of anti-hormone therapies for the treatment of patients with LS.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"42"},"PeriodicalIF":0.0,"publicationDate":"2014-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32774326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-10-04eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-41
Ana Cotta, Julia Filardi Paim, Antonio Lopes da-Cunha-Junior, Rafael Xavier Neto, Simone Vilela Nunes, Monica Magalhaes Navarro, Jaquelin Valicek, Elmano Carvalho, Lydia U Yamamoto, Camila F Almeida, Shelida Vasconcelos Braz, Reinaldo Issao Takata, Mariz Vainzof
{"title":"Limb girdle muscular dystrophy type 2G with myopathic-neurogenic motor unit potentials and a novel muscle image pattern.","authors":"Ana Cotta, Julia Filardi Paim, Antonio Lopes da-Cunha-Junior, Rafael Xavier Neto, Simone Vilela Nunes, Monica Magalhaes Navarro, Jaquelin Valicek, Elmano Carvalho, Lydia U Yamamoto, Camila F Almeida, Shelida Vasconcelos Braz, Reinaldo Issao Takata, Mariz Vainzof","doi":"10.1186/1472-6890-14-41","DOIUrl":"https://doi.org/10.1186/1472-6890-14-41","url":null,"abstract":"<p><strong>Background: </strong>Limb girdle muscular dystrophy type 2G (LGMD2G) is a subtype of autosomal recessive muscular dystrophy caused by mutations in the telethonin gene. There are few LGMD2G patients worldwide reported, and this is the first description associated with early tibialis anterior sparing on muscle image and myopathic-neurogenic motor unit potentials.</p><p><strong>Case presentation: </strong>Here we report a 31 years old caucasian male patient with progressive gait disturbance, and severe lower limb proximal weakness since the age of 20 years, associated with subtle facial muscle weakness. Computed tomography demonstrated soleus, medial gastrocnemius, and diffuse thigh muscles involvement with tibialis anterior sparing. Electromyography disclosed both neurogenic and myopathic motor unit potentials. Muscle biopsy demonstrated large groups of atrophic and hypertrophic fibers, frequent fibers with intracytoplasmic rimmed vacuoles full of autophagic membrane and sarcoplasmic debris, and a total deficiency of telethonin. Molecular investigation identified the common homozygous c.157C > T in the TCAP gene.</p><p><strong>Conclusion: </strong>This report expands the phenotypic variability of telethoninopathy/ LGMD2G, including: 1) mixed neurogenic and myopathic motor unit potentials, 2) facial weakness, and 3) tibialis anterior sparing. Appropriate diagnosis in these cases is important for genetic counseling and prognosis.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"41"},"PeriodicalIF":0.0,"publicationDate":"2014-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-41","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32731621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-10-01eCollection Date: 2015-01-01DOI: 10.1186/s12907-015-0002-8
Khaleel Al-Obaidy, Fatimah Alruwaii, Areej Al Nemer, Raed Alsulaiman, Zainab Alruwaii, Mohamed A Shawarby
{"title":"Primary gastric actinomycosis: report of a case diagnosed in a gastroscopic biopsy.","authors":"Khaleel Al-Obaidy, Fatimah Alruwaii, Areej Al Nemer, Raed Alsulaiman, Zainab Alruwaii, Mohamed A Shawarby","doi":"10.1186/s12907-015-0002-8","DOIUrl":"https://doi.org/10.1186/s12907-015-0002-8","url":null,"abstract":"","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"15 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12907-015-0002-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33134715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-09-12eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-40
Joanna J Moser, Marvin J Fritzler, Jerome B Rattner
{"title":"Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.","authors":"Joanna J Moser, Marvin J Fritzler, Jerome B Rattner","doi":"10.1186/1472-6890-14-40","DOIUrl":"https://doi.org/10.1186/1472-6890-14-40","url":null,"abstract":"<p><strong>Background: </strong>Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors.</p><p><strong>Methods: </strong>Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy.</p><p><strong>Results: </strong>We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium.</p><p><strong>Conclusions: </strong>Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously observed in cell cultures. This is the first study to demonstrate that defects in cilia expression and function are a true hallmark of GBM tumors and correlate with their unrestrained growth. A review of the current ultrastructural profiles in the literature provides suggestions as to the best possible candidate protein that underlies defects in the early stages of ciliogenesis within GBM tumors.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"40"},"PeriodicalIF":0.0,"publicationDate":"2014-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-40","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32674249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-09-05eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-39
Giorgio Perino, Benjamin F Ricciardi, Seth A Jerabek, Guido Martignoni, Gabrielle Wilner, Dan Maass, Steven R Goldring, P Edward Purdue
{"title":"Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study.","authors":"Giorgio Perino, Benjamin F Ricciardi, Seth A Jerabek, Guido Martignoni, Gabrielle Wilner, Dan Maass, Steven R Goldring, P Edward Purdue","doi":"10.1186/1472-6890-14-39","DOIUrl":"10.1186/1472-6890-14-39","url":null,"abstract":"<p><strong>Background: </strong>Adverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes.</p><p><strong>Methods: </strong>Consecutive patients presenting with ALTR from two major hip implant classes (N = 54 patients with Dual-Modular Neck implant; N = 14 patients with Metal-on-Metal implant) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy and cellular composition was assessed using immunohistochemistry.</p><p><strong>Results: </strong>Length of implantation was shorter in the DMN group versus MoM THA group (21.3 [8.4] months versus 43.6 [13.8] months respectively; p < 0.005) suggesting differences in implant performance. Morphologic examination revealed a common spectrum of neo-synovial proliferation and necrosis in both groups. Macrophages were more commonly present in diffuse sheets (Grade 3) in the MoM relative to DMN group (p = 0.016). Perivascular lymphocytes with germinal centers (Grade 4) were more common in the DMN group, which trended towards significance (p = 0.066). Qualitative differences in corrosion product morphology were seen between the two groups. Immunohistochemistry showed features of a CD4 and GATA-3 rich lymphocyte reaction in both implants, with increased ratios of perivascular T-cell relative to B-cell markers in the DMN relative to the MoM group (p = 0.032).</p><p><strong>Conclusion: </strong>Our results demonstrate that both implant classes display common features of neo-synovial proliferation and necrosis with a CD4 and GATA-3 rich inflammatory infiltrate. Qualitative differences in corrosion product appearance, macrophage morphology, and lymphocyte distributions were seen between the two implant types. Our data suggests that ALTR represents a histological spectrum with implant-based features.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"39"},"PeriodicalIF":0.0,"publicationDate":"2014-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32685121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-08-23eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-38
Anna M Wirsing, Oddveig G Rikardsen, Sonja E Steigen, Lars Uhlin-Hansen, Elin Hadler-Olsen
{"title":"Characterisation and prognostic value of tertiary lymphoid structures in oral squamous cell carcinoma.","authors":"Anna M Wirsing, Oddveig G Rikardsen, Sonja E Steigen, Lars Uhlin-Hansen, Elin Hadler-Olsen","doi":"10.1186/1472-6890-14-38","DOIUrl":"https://doi.org/10.1186/1472-6890-14-38","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinomas are often heavily infiltrated by immune cells. The organization of B-cells, follicular dendritic cells, T-cells and high-endothelial venules into structures termed tertiary lymphoid structures have been detected in various types of cancer, where their presence is found to predict favourable outcome. The purpose of the present study was to evaluate the incidence of tertiary lymphoid structures in oral squamous cell carcinomas, and if present, analyse whether they were associated with clinical outcome.</p><p><strong>Methods: </strong>Tumour samples from 80 patients with oral squamous cell carcinoma were immunohistochemically stained for B-cells, follicular dendritic cells, T-cells, germinal centre B-cells and high-endothelial venules. Some samples were sectioned at multiple levels to assess whether the presence of tertiary lymphoid structures varied within the tumour.</p><p><strong>Results: </strong>Tumour-associated tertiary lymphoid structures were detected in 21 % of the tumours and were associated with lower disease-specific death. The presence of tertiary lymphoid structures varied within different levels of a tissue block.</p><p><strong>Conclusions: </strong>Tertiary lymphoid structure formation was found to be a positive prognostic factor for patients with oral squamous cell carcinoma. Increased knowledge about tertiary lymphoid structure formation in oral squamous cell carcinoma might help to develop and guide immune-modulatory cancer treatments.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"38"},"PeriodicalIF":0.0,"publicationDate":"2014-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-38","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32631007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-08-09eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-37
Raju Adduri, Viswakalyan Kotapalli, Neha A Gupta, Swarnalata Gowrishankar, Mukta Srinivasulu, Mohammed Mujtaba Ali, Subramanyeshwar Rao, Shantveer G Uppin, Umanath K Nayak, Snehalatha Dhagam, Mohana Vamsy Chigurupati, Murali Dharan Bashyam
{"title":"P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue.","authors":"Raju Adduri, Viswakalyan Kotapalli, Neha A Gupta, Swarnalata Gowrishankar, Mukta Srinivasulu, Mohammed Mujtaba Ali, Subramanyeshwar Rao, Shantveer G Uppin, Umanath K Nayak, Snehalatha Dhagam, Mohana Vamsy Chigurupati, Murali Dharan Bashyam","doi":"10.1186/1472-6890-14-37","DOIUrl":"https://doi.org/10.1186/1472-6890-14-37","url":null,"abstract":"<p><strong>Background: </strong>Squamous cell carcinoma of tongue (SCCT) is expected to harbor unique clinico-pathological and molecular genetic features since a significant proportion of patients are young and exhibit no association with tobacco or alcohol.</p><p><strong>Methods: </strong>We determined P53, epidermal growth factor receptor, microsatellite instability, human papilloma virus infection and loss of heterozygosity status at several tumor suppressor loci in one hundred and twenty one oral SCCT (SSCOT) samples and analyzed their association with clinico-pathological features and patient survival.</p><p><strong>Results: </strong>Our results revealed a significantly higher incidence of p53 nuclear stabilization in early (as against late) onset SCCOT. FHIT loss was significantly associated with p53 nuclear stabilization and the association was stronger in patients with no history of tobacco use. Samples harboring mutation in p53 DNA binding domain or exhibiting p53 nuclear stabilization, were significantly associated with poor survival.</p><p><strong>Conclusion: </strong>Our study has therefore identified distinct features in SCCOT tumorigenesis with respect to age and tobacco exposure and revealed possible prognostic utility of p53.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"37"},"PeriodicalIF":0.0,"publicationDate":"2014-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32610457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-07-28eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-36
Suvi Lokka, Andreas H Scheel, Sebastian Dango, Katja Schmitz, Rudolf Hesterberg, Josef Rüschoff, Hans-Ulrich Schildhaus
{"title":"Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a report of two cases.","authors":"Suvi Lokka, Andreas H Scheel, Sebastian Dango, Katja Schmitz, Rudolf Hesterberg, Josef Rüschoff, Hans-Ulrich Schildhaus","doi":"10.1186/1472-6890-14-36","DOIUrl":"https://doi.org/10.1186/1472-6890-14-36","url":null,"abstract":"<p><strong>Background: </strong>Liposarcoma is the most frequent soft tissue sarcoma. Well differentiated liposarcoma may progress into dedifferentiated liposarcoma with pleomorphic histology. A minority additionally features myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of the Mouse double minute 2 homolog (MDM2) locus is characteristic for well differentiated and dedifferentiated liposarcomas. Detection of MDM2 amplification may supplement histopathology and aid to distinguish liposarcoma from other soft tissue neoplasia.</p><p><strong>Case presentation: </strong>Here we present two cases of dedifferentiated liposarcoma with challenging presentation. Case 1 features a myogenic component. As the tumour infiltrated the abdominal muscles and showed immunohistochemical expression of myogenic proteins, rhabdomyosarcoma had to be ruled out. Case 2 has an osteosarcomatous component resembling extraosseous osteosarcoma. The MDM2 status was determined in both cases and helped making the correct diagnosis. Overexpression of MDM2 and co-overexpression of Cyclin-dependent kinase 4 is demonstrated by immunohistochemistry. The underlying MDM2 amplification is shown by fluorescence in situ hybridisation. Since low grade osteosarcoma may also harbour MDM2 amplification it is emphasised that the amplification has to be present in the lipomatous parts of the tumour to distinguish liposarcoma from extraosseous osteosarcoma.</p><p><strong>Conclusions: </strong>The two cases exemplify challenges in the diagnoses of dedifferentiated liposarcoma. Liposarcoma often has pleomorphic histology and additionally may feature heterologous components that mimic other soft tissue neoplasms. Amplification of MDM2 is characteristic for well differentiated and dedifferentiated liposarcomas. Determination of the MDM2 status by in situ hybridisation may assist histopathology and help to rule out differential diagnoses.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"36"},"PeriodicalIF":0.0,"publicationDate":"2014-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32587387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-07-23eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-35
Asif Ali, Victoria Brown, Simon Denley, Nigel B Jamieson, Jennifer P Morton, Colin Nixon, Janet S Graham, Owen J Sansom, C Ross Carter, Colin J McKay, Fraser R Duthie, Karin A Oien
{"title":"Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel.","authors":"Asif Ali, Victoria Brown, Simon Denley, Nigel B Jamieson, Jennifer P Morton, Colin Nixon, Janet S Graham, Owen J Sansom, C Ross Carter, Colin J McKay, Fraser R Duthie, Karin A Oien","doi":"10.1186/1472-6890-14-35","DOIUrl":"10.1186/1472-6890-14-35","url":null,"abstract":"<p><strong>Background: </strong>Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.</p><p><strong>Methods: </strong>Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0-300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.</p><p><strong>Conclusion: </strong>A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"35"},"PeriodicalIF":0.0,"publicationDate":"2014-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32542551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC Clinical PathologyPub Date : 2014-07-15eCollection Date: 2014-01-01DOI: 10.1186/1472-6890-14-34
Will W Minuth, Lucia Denk
{"title":"Tannic acid label indicates abnormal cell development coinciding with regeneration of renal tubules.","authors":"Will W Minuth, Lucia Denk","doi":"10.1186/1472-6890-14-34","DOIUrl":"https://doi.org/10.1186/1472-6890-14-34","url":null,"abstract":"<p><strong>Background: </strong>Stem/progenitor cells are in the focus of research as a future therapeutic option to stimulate regeneration in diseased renal parenchyma. However, current data indicate that successful seeding of implanted stem/progenitor cells is prevented by harmful interstitial fluid and altered extracellular matrix. To find out possible parameters for cell adaptation, the present investigation was performed.</p><p><strong>Methods: </strong>Renal stem/progenitor cells were mounted in an artificial interstitium for perfusion culture. Exposure to chemically defined but CO2-independent culture media was tested during 13 days. Cell biological features were then analyzed by histochemistry, while structural details were investigated by transmission electron microscopy after conventional and improved fixation of specimens.</p><p><strong>Results: </strong>Culture of renal stem/progenitor cells as well in Leibovitz's L-15 Medium as CO2 Independent Medium shows in fluorescence microscopy spatial development of numerous tubules. Specimens of both media fixed by conventional glutaraldehyde exhibit in electron microscopy a homogeneous cell population in developed tubules. In contrast, fixation by glutaraldehyde including tannic acid illuminates that dispersed dark marked cells of unknown function are present. The screening further demonstrates that the dark cell type does not comply with cells found in embryonic, maturing or matured renal parenchyma.</p><p><strong>Conclusions: </strong>The actual data show that development of abnormal cell features must be taken into account, when regeneration of renal tubules is simulated under in vitro conditions.</p>","PeriodicalId":35804,"journal":{"name":"BMC Clinical Pathology","volume":"14 ","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2014-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6890-14-34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32542092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}