Cdx2 Protein Expression in Normal and Malignant Human Tissues: an Immunohistochemical Survey Using Tissue Microarrays Christopher A

Total Page:16

File Type:pdf, Size:1020Kb

Cdx2 Protein Expression in Normal and Malignant Human Tissues: an Immunohistochemical Survey Using Tissue Microarrays Christopher A Cdx2 Protein Expression in Normal and Malignant Human Tissues: An Immunohistochemical Survey Using Tissue Microarrays Christopher A. Moskaluk, M.D., Ph.D., Hong Zhang, M.D., Steven M. Powell, M.D., Lisa A. Cerilli, M.D., Garret M. Hampton, Ph.D., Henry F. Frierson, Jr., M.D. Departments of Pathology (CAM, LAC, HFF), of Biochemistry and Molecular Genetics (CAM), and of Medicine (SMP), University of Virginia Health System, Charlottesville, Virginia; Department of Pathology (HZ), Anhui Medical University, Hefei, China; and Genomics Institute of the Novartis Research Foundation (GMH), San Diego, California KEY WORDS: Cdx2, immunohistochemistry, RNA Cdx2 has been identified as a marker of colon can- profiling, Tissue microarray. cer in RNA-profiling experiments. We show here Mod Pathol 2003;16(9):913–919 that the detection of Cdx2 protein by immunohis- tochemistry correlates well with RNA transcript lev- Cdx2 is a homeobox gene that has been shown to els as detected by oligonucleotide microarrays. Us- play a role in the development of the small and ing tissue microarrays containing most normal large intestine in mammals and in the differentia- tissue types and an antibody to the Cdx2 protein, tion of intestinal epithelial cells. The Cdx2 gene is strong diffuse Cdx2 staining was only seen in the expressed in all but the most distal portions of the nuclei of small and large intestinal epithelium and intestinal tract during development (1, 2). In a cell portions of the pancreatic duct system. In tissue culture model, Cdx2 has been shown to decrease microarrays containing 745 cancers from many an- cellular replication and induce differentiation to atomic sites, colonic adenocarcinomas showed mature intestinal epithelium (3). Cdx2 acts as a strong extensive staining in 90% of cases, with ade- transcription factor, increasing the expression of nocarcinomas of the stomach, esophagus, and several gene products associated with mature intes- ovary (endometrioid and mucinous types) showing tinal epithelial cells (3, 4). Perhaps not surprisingly, extensive staining in only 20–30% of cases. Other Cdx2 has recently been identified as a gene whose types of carcinomas showed extensive staining in expression had a high predictive value for the diag- only <1% of cases. Of 30 neuroendocrine tumors nosis of colonic adenocarcinoma in microarray examined, carcinoids of the midgut and hindgut gene expression analyses (5, 6). The use of Cdx2 as had the most cases with extensive staining (73% and an immunohistochemical marker has been de- 44%, respectively), thus paralleling the distribution scribed recently in studies of human gastric and of Cdx2 expression in adenocarcinomas. Cdx2 colon cancer, but no comprehensive survey of Cdx2 shows a limited range of expression in the spectrum protein expression has been reported (7–9). To fol- of human tissues and neoplasia and thus may have low up on previous RNA transcript profiling data, utility in determining the site of origin of tumors in we report our findings using immunohistochemis- certain clinical situations. try on tissue microarrays to comprehensively pro- file the protein expression of Cdx2 in a broad range of human carcinomas and normal tissues. Copyright © 2003 by The United States and Canadian Academy of Pathology, Inc. VOL. 16, NO. 9, P. 913, 2003 Printed in the U.S.A. MATERIALS AND METHODS Date of acceptance: May 29, 2003. Hong Zhang is an ITREID fellow in the Center for Global Health at The University of Virginia and is supported by NIH Fogerty Grant Tissue Specimens D43TW00909-05. Address reprint requests to: Christopher A. Moskaluk, M.D., Ph.D., De- Formalin-fixed, paraffin-embedded tissue blocks partment of Pathology, University of Virginia Health System, Rm. 3890 were obtained from the archives of the Department Old Medical School Bldg., Jefferson Park Ave., Charlottesville, VA 22908; fax: 434-243-6757; e-mail: [email protected]. of Pathology of the University of Virginia Health DOI: 10.1097/01.MP.0000086073.92773.55 System with institutional review board approval. 913 Tissue Microarrays TABLE 1. Cdx2 Immunohistochemical Staining in Normal Tissues Targeted tissue areas were marked on H&E- No staining Peripheral nerve stained sections corresponding to the paraffin Adipocytes Pituitary blocks. One to three 0.6-mm tissue cores from each Adrenal cortex Placental membranes case were removed using a manual microarray de- Adrenal medulla Placental villi Anal squamous epithelium Prostate vice (Beecher Instruments, Silver Spring, MD) and Astroglia Salivary gland, minor inserted into recipient paraffin blocks. The tissue Bartholin gland Salivary gland, parotid microarrays were sectioned at a 4-␮m thickness Bile duct epithelium Salivary gland, submandibular Bladder transitional epithelium Seminal vesicle and placed on charged slides. Blood vessels Skeletal muscle Bone Skin, squamous epithelium Bone marrow Skin, sweat glands Breast (duct epithelium) Smooth muscle, uterus Immunohistochemistry Breast (lobular epithelium) Spinal cord Bronchial epithelium Spleen Tissue microarray and standard tissue histologic Brunner glands Stomach, antrum sections were deparaffinized, rehydrated, and Cartilage (bronchus) Stomach, fundus Endocervical epithelium Synovium blocked with methanolic 3% hydrogen peroxide. Endometrial epithelium, Tendon The slides were immersed in 10 mM citrate buffer, proliferative pH 6.0 and heated in a 1200W microwave oven at Endometrial epithelium, secretory Testis, Leydig cells Endometrial stroma Testis, rete the highest power setting. Evaporated liquid was Endometrial stroma, decidualized Testis, seminiferous tubules replenished at 5 minutes, then the slides were Epidiymis Thymus heated at high power for an additional 5 minutes. Esophagus, squamous epithelium Thyroid Esophagus, submucosal glands Tonsil The slides were left in the buffer for an additional 10 Fallopian tube Ureter minutes before being removed. The antibody used Gallbladder Urethra, male was a mouse monoclonal antibody raised against Ganglia, peripheral Vagina, squamous epithelium Heart, myocardium Vas deferens full-length recombinant Cdx2 protein (AM392—5 M; Kidney, cortex Vulva, squamous epithelium BioGenex, San Ramon, CA). Immunostaining was Kidney, medulla Umbilical cord performed by hand using the prediluted antibody Lacrimal gland Liver, hepatocytes 2ϩ staining solution and a 30-minute incubation. After wash- Liver, portal tracts Pancreatic ducts, intermediate ing, antibody binding was visualized using the to large cts avidin-biotin-peroxidase technique (Vectastain Lung alveoli Lymph node 4ϩ staining Elite ABC kit, Vector Laboratories, Burlington, VT), Lymphatics Appendiceal epithelium followed by incubation with 3,3'-diaminobenzidine Melanocytes Colonic epithelium tetrahydrochloride. The slides were counterstained Mesothelium Pancreatic centroacinar cells Neurons (cerebellum) Pancreatic ducts, interacinar with hematoxylin. Neurons (cerebrum) Rectal epithelium The immunohistochemical stains were evalu- Ovarian stroma Small intestinal epithelium ated by two pathologists (HFF and CAM). Only Ovary, corpus luteum Ovary, primary follicle and germ nuclear staining was considered positive, and it cells was scored on the following basis: 0 (no detect- Pancreatic acinar cells able staining); 1ϩ (Ͻ25% positive cells); 2ϩ (25– Pancreatic islets Parathyroid 49%); 3ϩ (50–74%); 4ϩ (Ͼ75%). In general, cases showing 3ϩ and 4ϩ staining also had strong in- tense staining, so intensity was not factored into the scoring. RNA Gene Expression Profiling The list of normal tissues examined is given in Gene expression profiles of a subset of tumor Table 1. Focal heterogeneous Cdx2 expression cases were obtained on U95a GeneChips (Af- was present in the pancreatic tissue microarray fymetrix, Santa Clara, CA), as reported previously samples, and standard histologic sections of this (6). organ were also examined for confirmation of this finding. RESULTS The list of tumors examined is given in Table 2. The following tumors were absent from or not The degree of Cdx2 protein expression, as deter- well represented in the arrays, and additional mined by immunohistochemistry, was compared cases were obtained and examined as standard with the level of Cdx2 RNA transcript levels for a histologic sections: germ cell tumors (12 addi- subset of tumors. Transcript levels determined by tional cases), ampullary carcinoma (6 cases), and hybridization to GeneChip oligonucleotide arrays neuroendocrine carcinomas of the gastrointesti- (Affymetrix Inc.) were available for 20 breast ade- nal tract, biliary tract, lung, and pancreas (30 nocarcinomas, 19 colon adenocarcinomas, 2 gastric cases). adenocarcinomas, 12 lung adenocarcinomas, 12 914 Modern Pathology TABLE 2. Immunohistochemical Staining of Cancers Staining Pattern 0 1ϩ 2ϩ 3ϩ 4ϩ Ampullary carcinoma 21111 Bladder/ureter transitional cell carcinoma 70000 Breast adenocarcinoma 70 0000 Carcinoid tumors Lung 52000 Common bile duct 11000 Foregut (stomach) 30000 Midgut (ileum & appendix) 00117 Hindgut (rectum) 22131 Cholangiocarcinoma 87200 Colorectal adenocarcinoma 042549 Gallbladder adenocarcinoma 42000 Gastroesophageal adenocarcinoma 88 23 20 15 18 Germ cell tumors Dysgerminoma 31000 Embryonal Carcinoma 30000 Seminoma 60000 Yolk sac tumor 11210 Hepatocellular carcinoma 12 0000 Lung carcinoma Adenocarcinoma 33 1100 Large cell undifferentiated carcinoma 10000 Small cell/Neuroendocrine carcinoma 20000 Squamous cell carcinoma 13 0000 Melanoma 10000 Mesothelioma 28 0000 Ovarian tumors Clear cell ca 11000 Endometrioid
Recommended publications
  • Te2, Part Iii
    TERMINOLOGIA EMBRYOLOGICA Second Edition International Embryological Terminology FIPAT The Federative International Programme for Anatomical Terminology A programme of the International Federation of Associations of Anatomists (IFAA) TE2, PART III Contents Caput V: Organogenesis Chapter 5: Organogenesis (continued) Systema respiratorium Respiratory system Systema urinarium Urinary system Systemata genitalia Genital systems Coeloma Coelom Glandulae endocrinae Endocrine glands Systema cardiovasculare Cardiovascular system Systema lymphoideum Lymphoid system Bibliographic Reference Citation: FIPAT. Terminologia Embryologica. 2nd ed. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology, February 2017 Published pending approval by the General Assembly at the next Congress of IFAA (2019) Creative Commons License: The publication of Terminologia Embryologica is under a Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) license The individual terms in this terminology are within the public domain. Statements about terms being part of this international standard terminology should use the above bibliographic reference to cite this terminology. The unaltered PDF files of this terminology may be freely copied and distributed by users. IFAA member societies are authorized to publish translations of this terminology. Authors of other works that might be considered derivative should write to the Chair of FIPAT for permission to publish a derivative work. Caput V: ORGANOGENESIS Chapter 5: ORGANOGENESIS
    [Show full text]
  • Acinic Cell Carcinoma with Extensive Neuroendocrine Differentiation: a Diagnostic Challenge
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central Head and Neck Pathol (2009) 3:163–168 DOI 10.1007/s12105-009-0114-5 CASE REPORT Acinic Cell Carcinoma with Extensive Neuroendocrine Differentiation: A Diagnostic Challenge Somak Roy Æ Kajal Kiran Dhingra Æ Parul Gupta Æ Nita Khurana Æ Bulbul Gupta Æ Ravi Meher Received: 30 January 2009 / Accepted: 11 March 2009 / Published online: 26 March 2009 Ó Humana 2009 Abstract Primary salivary gland carcinoma with neuro- Keywords Neuroendocrine Á Acinic cell Á Warthin’s Á endocrine differentiation is of rare occurrence, especially Chromogranin Á Carcinoma Á Parotid so in the parotid gland. Amongst the various reported pri- mary tumors with neuroendocrine differentiation, acinic cell carcinoma (ACC) one such tumor. A 48 year old lady Introduction presented with a gradually increasing right infra-auricular swelling for a period of 1 year which enlarged suddenly in Primary salivary gland carcinomas with neuroendocrine a short period. Contrast Enhanced Computed Tomography differentiation are rare accounting for 3.5% of all malig- (CECT) suggested diagnosis of Pleomorphic Adenoma. nant tumors and less than 1% of all carcinomas of parotid Fine Needle Aspiration Cytology (FANC) yielded a cystic gland [1]. Nicod reported the first case of carcinoid tumor fluid suggesting a possibility of Warthin’s tumor or of the parotid gland in a 51 year old lady [2]. Following Oncocytic lesion. Intraoperative findings were suggestive this there have been occasional reports of round cell tumors of a Warthin’s tumor. Initial histopathological examination of the parotid gland and minor salivary glands with very of the tumor was suggestive of neuroendocrine carcinoma.
    [Show full text]
  • Prospective Isolation of NKX2-1–Expressing Human Lung Progenitors Derived from Pluripotent Stem Cells
    The Journal of Clinical Investigation RESEARCH ARTICLE Prospective isolation of NKX2-1–expressing human lung progenitors derived from pluripotent stem cells Finn Hawkins,1,2 Philipp Kramer,3 Anjali Jacob,1,2 Ian Driver,4 Dylan C. Thomas,1 Katherine B. McCauley,1,2 Nicholas Skvir,1 Ana M. Crane,3 Anita A. Kurmann,1,5 Anthony N. Hollenberg,5 Sinead Nguyen,1 Brandon G. Wong,6 Ahmad S. Khalil,6,7 Sarah X.L. Huang,3,8 Susan Guttentag,9 Jason R. Rock,4 John M. Shannon,10 Brian R. Davis,3 and Darrell N. Kotton1,2 2 1Center for Regenerative Medicine, and The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. 3Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA. 4Department of Anatomy, UCSF, San Francisco, California, USA. 5Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. 6Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, Massachusetts, USA. 7Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA. 8Columbia Center for Translational Immunology & Columbia Center for Human Development, Columbia University Medical Center, New York, New York, USA. 9Department of Pediatrics, Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee, USA. 10Division of Pulmonary Biology, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA. It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1–expressing (NKX2-1+) precursor cells.
    [Show full text]
  • Reciprocal Regulation of TEAD4 and CCN2 for the Trophectoderm Development of the Bovine Blastocyst
    155 6 REPRODUCTIONRESEARCH Reciprocal regulation of TEAD4 and CCN2 for the trophectoderm development of the bovine blastocyst Hiroki Akizawa1,2, Ken Kobayashi3, Hanako Bai1, Masashi Takahashi1, Shinjiro Kagawa1, Hiroaki Nagatomo1,† and Manabu Kawahara1 1Laboratory of Animal Genetics and Reproduction, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan, 2Japan Society for the Promotion of Science (JSPS Research Fellow), Tokyo, Japan and 3Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan Correspondence should be addressed to M Kawahara; Email: [email protected] †(Hiroaki Nagatomo is now at Department of Biotechnology, Faculty of Life and Environmental Science, University of Yamanashi, Kofu, Japan) Abstract The first segregation at the blastocyst stage is the symmetry-breaking event to characterize two cell components; namely, inner cell mass (ICM) and trophectoderm (TE). TEA domain transcription factor 4 (TEAD4) is a well-known regulator to determine TE properties of blastomeres in rodent models. However, the roles of bovine TEAD4 in blastocyst development have been unclear. We here aimed to clarify the mechanisms underlining TE characterization by TEAD4 in bovine blastocysts. We first found that the TEAD4 mRNA expression level was greater in TE than in ICM, which was further supported by TEAD4 immunofluorescent staining. Subsequently, we examined the expression patterns of TE-expressed genes; CDX2, GATA2 and CCN2, in the TEAD4-knockdown (KD) blastocysts. These expression levels significantly decreased in the TEAD4 KD blastocysts compared with controls. Of these downregulated genes, the CCN2 expression level decreased the most. We further analyzed the expression levels of TE-expressed genes; CDX2, GATA2 and TEAD4 in the CCN2 KD blastocysts.
    [Show full text]
  • Regulation of the Tumor Suppressor Homeogene Cdx2 by Hnf4a in Intestinal Cancer
    Oncogene (2013) 32, 3782–3788 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc SHORT COMMUNICATION Regulation of the tumor suppressor homeogene Cdx2 by HNF4a in intestinal cancer T Saandi1,2, F Baraille3,4,5, L Derbal-Wolfrom1,2, A-L Cattin3,4,5, F Benahmed1,6, E Martin1,2, P Cardot3,4,5, B Duclos1,2,7, A Ribeiro3,4,5, J-N Freund1,2,8 and I Duluc1,2,8 The gut-specific homeotic transcription factor Cdx2 is a crucial regulator of intestinal development and homeostasis, which is downregulated in colorectal cancers (CRC) and exhibits a tumor suppressor function in the colon. We have previously established that several endodermal transcription factors, including HNF4a and GATA6, are involved in Cdx2 regulation in the normal gut. Here we have studied the role of HNF4a in the mechanism of deregulation of Cdx2 in colon cancers. Crossing ApcD14/ þ mice prone to spontaneous intestinal tumor development with pCdx2-9LacZ transgenic mice containing the LacZ reporter under the control of the 9.3-kb Cdx2 promoter showed that this promoter segment contains sequences recapitulating the decrease of Cdx2 expression in intestinal cancers. Immunohistochemistry revealed that HNF4a, unlike GATA6, exhibited a similar decrease to Cdx2 in genetic (Apcmin/ þ and ApcD14/ þ ) and chemically induced (Azoxymethane (AOM) treatment) models of intestinal tumors in mice. HNF4a and Cdx2 also exhibited a comparable deregulated pattern in human CRC. Correlated patterns were observed between HNF4a and Cdx2 in several experimental models of human colon cancer cell lines: xenografts in nude mice, wound healing and glucose starvation.
    [Show full text]
  • Role of Cdx Factors in Early Mesodermal Fate Decisions Tanya E
    © 2019. Published by The Company of Biologists Ltd | Development (2019) 146, dev170498. doi:10.1242/dev.170498 RESEARCH ARTICLE Role of Cdx factors in early mesodermal fate decisions Tanya E. Foley, Bradley Hess, Joanne G. A. Savory, Randy Ringuette and David Lohnes* ABSTRACT Cdx1−/− or Cdx2+/− phenotypes, indicative of functional overlap Murine cardiac and hematopoietic progenitors are derived from Mesp1+ between Cdx family members (Faas and Isaacs, 2009; Savory et al., mesoderm. Cdx function impacts both yolk sac hematopoiesis and 2011; van den Akker et al., 2002; van Nes et al., 2006; Young et al., Cdx2 cardiogenesis in zebrafish, suggesting that Cdx family members 2009). The derivation and analysis of conditional mutants regulate early mesoderm cell fate decisions. We found that Cdx2 (Savory et al., 2009a; Stringer et al., 2012) and compound mutant occupies a number of transcription factor loci during embryogenesis, derivatives (van den Akker et al., 2002; Savory et al., 2011; Verzi including key regulators of both cardiac and blood development, and et al., 2011; van Rooijen et al., 2012; Stringer et al., 2012; Grainger that Cdx function is required for normal expression of the cardiogenic et al., 2010; Hryniuk et al., 2012) further substantiated the transcription factors Nkx2-5 and Tbx5. Furthermore, Cdx and Brg1, an functional overlap between family members. Analysis of these ATPase subunit of the SWI/SNF chromatin remodeling complex, co- mutants also revealed a requirement for Cdx genes in diverse occupy a number of loci, suggesting that Cdx family members regulate processes in development and in the adult intestinal track. These target gene expression through alterations in chromatin architecture.
    [Show full text]
  • Epithelium 2 : Glandular Epithelium Histology Laboratory -­‐ Year 1, Fall Term Dr
    Epithelium 2 : Glandular Epithelium Histology Laboratory -­‐ Year 1, Fall Term Dr. Heather Yule ([email protected]) October 21, 2014 Slides for study: 75 (Salivary Gland), 355 (Pancreas Tail), 48 (Atrophic Mammary Gland), 49 (Active Mammary Gland) and 50 (Resting Mammary Gland) Electron micrographs for : study EM: Serous acinus in parotid gland EM: Mucous acinus in mixed salivary gland EM: Pancreatic acinar cell Main Objective: Understand key histological features of glandular epithelium and relate structure to function. Specific Objectives: 1. Describe key histological differences between endocrine and exocrine glands including their development. 2. Compare three modes of secretion in glands; holocrine, apocrine and merocrine. 3. Explain the functional significance of polarization of glandular epithelial cells. 4. Define the terms parenchyma, stroma, mucous acinus, serous acinus and serous a demilune and be able to them identify in glandular tissue. 5. Distinguish exocrine and endocrine pancreas. 6. Compare the histology of resting, lactating and postmenopausal mammary glands. Keywords: endocrine gland, exocrine gland, holocrine, apocrine, merocrine, polarity, parenchyma, stroma, acinus, myoepithelial cell, mucous gland, serous gland, mixed or seromucous gland, serous demilune, exocrine pancreas, endocrine pancreas (pancreatic islets), resting mammary gland, lactating mammary gland, postmenopausal mammary gland “This copy is made solely for your personal use for research, private study, education, parody, satire, criticism, or review
    [Show full text]
  • Report of a Case of Acinic Cell Carcinoma of the Upper Lip and Review of Japanese Cases of Acinic Cell Carcinoma of the Minor Salivary Glands
    J Clin Exp Dent-AHEAD OF PRINT Acinic cell carcinoma of the minor salivary glands Journal section: Oral Surgery doi:10.4317/jced.53049 Publication Types: Case Report http://dx.doi.org/10.4317/jced.53049 Report of a case of acinic cell carcinoma of the upper lip and review of Japanese cases of acinic cell carcinoma of the minor salivary glands Shigeo Ishikawa 1, Hitoshi Ishikawa 2, Shigemi Fuyama 3, Takehito Kobayashi 4, Takayoshi Waki 5, Yukio Taira 4, Mitsuyoshi Iino 1 1 Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan 2 Yamagata Saisei Hospital, Department of Health Information Management, 79-1 Oki-machi, Yamagata 990-8545, Japan 3 Department of Diagnostic Pathology, Okitama Public General Hospital, 2000 Nishi-Otsuka, Kawanishi, Higashi-Okitama-gun, Yamagata 992-0601, Japan 4 Department of Dentistry, Oral and Maxillofacial Surgery, Okitama Public General Hospital, 2000 Nishi-Otsuka, Kawanishi, Higashi-Okitama-gun, Yamagata 992-0601, Japan 5 Department of Otolaryngology and Head and Neck Surgery, Okitama Public General Hospital, 2000 Nishi-Otsuka, Kawanishi, Higashi-Okitama-gun, Yamagata 992-0601, Japan Correspondence: Department of Dentistry, Oral and Maxillofacial Plastic and Reconstructive Surgery Faculty of Medicine, Yamagata University 2-2-2 Iida-nishi, Yamagata 990-9585, Japan [email protected] Please cite this article in press as: Ishikawa S, Ishikawa H, Fuyama S, Received: 17/02/2016 Kobayashi T, Waki T, Taira Y, Iino M. ������������������������������������Report of a case of acinic cell car- Accepted: 15/04/2016 cinoma of the upper lip and review of japanese cases of acinic cell carci- noma of the minor salivary glands.
    [Show full text]
  • CDX2 As a Useful Marker of Colorectal Adenocarcinoma Metastases to Lung in Pre-Operative Biopsy Specimens
    87-92 1/6/07 12:56 Page 87 ONCOLOGY REPORTS 18: 87-92, 2007 87 CDX2 as a useful marker of colorectal adenocarcinoma metastases to lung in pre-operative biopsy specimens SHIGEBUMI TANAKA1, KANA SAITO1,2, TOMOKAZU ITO1, KOHEI TAJIMA3, AKIRA MOGI3, YOSHINORI SHITARA4, TAKAAKI SANO2 and HIROYUKI KUWANO1 Departments of 1General Surgical Science, 2Tumor Pathology, Gunma Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511; 3Department of Surgery, Fujioka General Hospital, 942-1 Fujioka, Fujioka, Gunma 375-8503; 4Department of Surgery, Isesaki General Hospital, 12-1 Tsunatorihoncho, Isesaki, Gunma 372-0821, Japan Received January 12, 2007; Accepted April 17, 2007 Abstract. Although distinguishing metastatic colorectal as a solitary nodule. Differential diagnosis between metastatic adenocarcinoma from primary lung adenocarcinoma is often adenocarcinoma of colorectal origin and primary lung adeno- difficult, pre- or intra-operative identification is very important, carcinoma using imaging techniques such as chest computed as the resection areas for each diagnosis differ substantially. tomography (CT) is thus often difficult in patients with a CDX2, a recently cloned homeobox gene, represents a highly history of colorectal cancer. However, this differentiation is specific and sensitive marker of colorectal adenocarcinoma. crucial for therapeutic and prognostic purposes (1). Particularly We evaluated CDX2 expression using pre- and intra-operative in cases with operative indications, pre- or intra-operative biopsy specimens. The study examined 50 consecutive colo- identification is very important, as the resection areas differ rectal adenocarcinoma metastases to the lung, including 20 substantially between the diagnoses. If the tumor is a solitary biopsy specimens and 66 resected specimens, and 21 primary metastatic colorectal carcinoma to the lung, partial lung lung adenocarcinomas.
    [Show full text]
  • An Analysis of Benign Human Prostate Offers Insights Into the Mechanism
    www.nature.com/scientificreports OPEN An analysis of benign human prostate ofers insights into the mechanism of apocrine secretion Received: 12 March 2018 Accepted: 22 February 2019 and the origin of prostasomes Published: xx xx xxxx Nigel J. Fullwood 1, Alan J. Lawlor2, Pierre L. Martin-Hirsch3, Shyam S. Matanhelia3 & Francis L. Martin 4 The structure and function of normal human prostate is still not fully understood. Herein, we concentrate on the diferent cell types present in normal prostate, describing some previously unreported types and provide evidence that prostasomes are primarily produced by apocrine secretion. Patients (n = 10) undergoing TURP were prospectively consented based on their having a low risk of harbouring CaP. Scanning electron microscopy and transmission electron microscopy was used to characterise cell types and modes of secretion. Zinc levels were determined using Inductively Coupled Plasma Mass Spectrometry. Although merocrine secretory cells were noted, the majority of secretory cells appear to be apocrine; for the frst time, we clearly show high-resolution images of the stages of aposome secretion in human prostate. We also report a previously undescribed type of epithelial cell and the frst ultrastructural image of wrapping cells in human prostate stroma. The zinc levels in the tissues examined were uniformly high and X-ray microanalysis detected zinc in merocrine cells but not in prostasomes. We conclude that a signifcant proportion of prostasomes, possibly the majority, are generated via apocrine secretion. This fnding provides an explanation as to why so many large proteins, without a signal peptide sequence, are present in the prostatic fuid. Tere are many complications associated with the prostate from middle age onwards, including benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
    [Show full text]
  • Evaluation of PAX2 and PAX8 Expression in Salivary Gland Neoplasms
    Head and Neck Pathol (2015) 9:47–50 DOI 10.1007/s12105-014-0546-4 ORIGINAL PAPER Evaluation of PAX2 and PAX8 Expression in Salivary Gland Neoplasms Randall T. Butler • Megan A. Alderman • Lester D. R. Thompson • Jonathan B. McHugh Received: 3 March 2014 / Accepted: 16 April 2014 / Published online: 26 April 2014 Ó Springer Science+Business Media New York 2014 Abstract PAX2 and PAX8 are transcription factors Introduction involved in embryogenesis that have been utilized as immunohistochemical indicators of tumor origin. Specifi- The PAX genes encode a family of nine transcription fac- cally, PAX2 is a marker of neoplasms of renal and tors, defined by the presence of a 128-amino acid DNA- mu¨llerian origin, while PAX8 is expressed by renal, binding sequence called the ‘‘paired domain,’’ that have mu¨llerian, and thyroid tumors. While studies examining been shown to play integral roles in development and these transcription factors in a variety of tumors have been maintenance of pluripotent stem cells [1]. PAX2 and PAX8 published, data regarding their expression in salivary gland are members of the same subfamily and are involved in neoplasms are limited. The goal of this study was to assess organogenesis of the central nervous, genitourinary, and expression of PAX2 and PAX8 in a large cohort of salivary mu¨llerian systems, with PAX8 additionally involved in gland tumors. Utilizing tissue microarrays, samples of development of the thyroid gland [1]. Correspondingly, normal salivary glands (n = 68) and benign and malignant immunohistochemical detection of PAX2 and/or PAX8 salivary gland neoplasms (n = 442) were evaluated for expression has emerged as an important diagnostic tool in nuclear immunoreactivity with PAX2 and PAX8.
    [Show full text]
  • Epithelium and Glands
    EPITHELIUM AND GLANDS OBJECTIVES: After completing this exercise, students should be able to do the following: 1. Identify glands. 2. Classify glands based on secretory type. ASSIGNMENT FOR TODAY'S LABORATORY GLASS SLIDES SL 111 (Trachea) cilia and unicellular glands (goblet cells) SL 019 (Jejunum, PAS) unicellular glands SL 092 (Submandibular gland) serous, mucous and demilune secretory units SL 093 (Sublingual gland) mucous secretory units POSTED ELECTRON MICROGRAPHS # 7 Organelles # 11 Desmosomes # 12 Epithelium # 13 Freeze-fracture Lab 5 Posted EMs; Lab 5 Posted EMs with some yellow labels SUPPLEMENTAL MATERIAL: SUPPLEMENTARY ELECTRON MICROGRAPHS Rhodin, J. A.G., An Atlas of Histology. Glands pp. 46 - 52 Copies of this text are on reserve in the HSL. Glandular epithelium is specialized for the production and secretion of products. The cells that form glands are usually cuboidal or columnar in shape. In this exercise we are emphasizing morphological differences in glands with respect to secretory products. A. UNICELLULAR GLANDS: SL 111 (low, high), (Trachea, H&E); SL 019 (oil), (Jejunum, PAS), for review. Goblet cells may be few or numerous and are found in epithelia of the respiratory and alimentary systems. The secretory product is emptied into the lumen of the organ rather than into ducts (J. Fig. 4-18, 15-24; R. 5.38, Plate 60) B. MULTICELLULAR GLANDS: In general these glands are formed by invagination, proliferation, and differentiation of the epithelium from which they are derived. Glands that maintain a connection with the surface epithelium through ducts are termed exocrine glands, whereas glands that have lost this connection, and secrete instead to blood vessels, are called endocrine glands (see J.
    [Show full text]