Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 21 March 2000

Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms

  • S Munakata1,
  • T Enomoto2,
  • M Tsujimoto3,
  • Y Otsuki4,
  • H Miwa1,
  • H Kanno1 &
  • …
  • K Aozasa1 

British Journal of Cancer volume 82, pages 1446–1452 (2000)Cite this article

  • 931 Accesses

  • 69 Citations

  • Metrics details

This article has been updated

Abstract

Expression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM (P< 0.05) and 12 of 63 (19%) with carcinoma (P< 0.05). Cases with bcl-2 expression showed more favourable prognosis than those without, but the difference was not statistically significant. There was no difference in frequency of Bax and Fas expression between each histologic category. Fas L expression was observed in one of 36 cases (3%) with adenoma, but in 12 of 33 (36%) with LPM (P< 0.001) and 42 of 63 (67%) with carcinoma (P< 0.0001). In carcinomas, cases expressing Fas L showed a less favourable prognosis than those without (P= 0.02). Density of CD8+ lymphocytes, possibly cytotoxic T-cells, was higher in serous carcinoma with negative Fas L expression than those with positive Fas L expression. These findings suggest that Fas L expressing carcinomas induce apoptosis in infiltrating CTL with Fas expression, and escape from immune surveillance. © 2000 Cancer Research Campaign

Similar content being viewed by others

Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer

Article Open access 14 October 2023

Mechano-inhibition of endocytosis sensitizes cancer cells to Fas-induced Apoptosis

Article Open access 22 June 2024

Evolutionary regulation of human Fas ligand (CD95L) by plasmin in solid cancer immunotherapy

Article Open access 01 July 2025

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Armitage BG (1987) Statistical Methods in Medical Research 2nd edn. Blackwell: Oxford

    Google Scholar 

  • Barber HRK (1993) Ovarian Carcinoma. Etiology, Diagnosis, and Treatment 3rd edn. Springer-Verlag: New York

    Book  Google Scholar 

  • Bennett MW, O'Connell J, O'Sullivan GC, Brady C, Roche D, Collins JK and Shanahan F (1998) The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol 160: 5669–5675

    CAS  PubMed  Google Scholar 

  • Brambilla E, Negoescu A, Gazzeri S, Lantuejoul S, Moro D, Brambilla C and Coll JL (1996) Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol 149: 1941–1952

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brinton LA and Hoover RN (1992) Epidemiology of gynecologic cancers. In: Principles and Practice of Gynecologic Oncology Hoskins WJ, Perez CA, Young RC (eds), pp. 3–26, JB Lippincott: Philadelphia

    Google Scholar 

  • Garzetti GG, Ciavattini A, Goteri G, Nictolis MD, Stramazzotti D, Lucarini G and Biagini G (1995) Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: index of proliferative activity with prognostic significance. Gynecol Oncol 56: 169–174

    Article  CAS  Google Scholar 

  • Hahne M, Rimoldi D, Schröter M, Romero P, Schreier M, French LE, Schneider P, Bornand T, Fontana A, Lienard D, Cerottini JC and Tschopp J (1996) Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science 274: 1363–1366

    Article  CAS  Google Scholar 

  • Hellquist HB, Olejnicka B, Jadner M, Andersson T and Sederholm C (1997) Fas receptor is expressed in human lung squamous cell carcinomas, whereas bcl-2 and apoptosis are not pronounced: a preliminary report. Br J Cancer 76: 175–179

    Article  CAS  Google Scholar 

  • Henriksen R, Funa K, Wilander E, Bäckström T, Ridderheim M and Öberg K (1993) Expression and prognostic significance of platelet-derived growth factor and its receptors in epithelial ovarian neoplasms. Cancer Res 53: 4550–4554

    CAS  PubMed  Google Scholar 

  • Henriksen R, Wilander E and Öberg K (1995) Expression and prognostic significance of Bcl-2 in ovarian tumours. Br J Cancer 72: 1324–1329

    Article  CAS  Google Scholar 

  • Hockenbery D, Nuñez G, Milliman C, Shreiber RD and Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334–336

    Article  CAS  Google Scholar 

  • Hoehner JC, Gestblom C, Olsen L and Påhlman S (1997) Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. Br J Cancer 75: 1185–1194

    Article  CAS  Google Scholar 

  • Hughes SJ, Nambu Y, Soldes OS, Hamstra D, Rehemtulla A, Iannettoni MD, Orringer MB and Beer DG (1997) Fas/APO-1 (CD95) is not translocated to the cell membrane in esophageal adenocarcinoma. Cancer Res 57: 5571–5578

    CAS  PubMed  Google Scholar 

  • Joensuu H, Pylkkänen L and Toikkanen S (1994) Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol 145: 1191–1198

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan EL and Meier P (1958) Non-parametric estimation from incomplete observations. J Am Stat Ass 53: 457–481

    Article  Google Scholar 

  • Katsube Y, Berg JW and Silverberg SG (1982) Epidemiologic pathology of ovarian tumors: a histopathologic review of primary ovarian neoplasms diagnosed in the Denver Standard Metropolitan Statistical Area, 1 July–31 December 1969 and 1 July–31 December 1979. Int J Gynecol Pathol 1: 3–16

    Article  CAS  Google Scholar 

  • Koonings PP, Campbell K, Mishell DR and Grimes DA (1989) Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol 74: 921–926

    CAS  PubMed  Google Scholar 

  • Landowski TH, Qu N, Buyuksal I, Painter JS and Dalton WS (1997) Mutations in the Fas antigen in patients with multiple myeloma. Blood 90: 4266–4270

    CAS  PubMed  Google Scholar 

  • McDonnell TJ, Deane N, Platt FM, Nunez G, Jaeger U, Mckearn JP and Korsmeyer SJ (1989) Bcl-2 immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell 57: 79–88

    Article  CAS  Google Scholar 

  • Müllauer L, Mosberger I and Chott A (1998) Fas ligand expression in nodal non-Hodgkin's lymphoma. Mod Pathol 11: 369–375

    PubMed  Google Scholar 

  • Nagata S and Golstein P (1995) The Fas death factor. Science 267: 1449–1456

    Article  CAS  Google Scholar 

  • Niehans GA, Brunner T, Frizelle SP, Liston JC, Salerno CT, Knapp DJ, Green DR and Kratzke RA (1997) Human lung carcinomas express Fas ligand. Cancer Res 57: 1007–1012

    CAS  PubMed  Google Scholar 

  • Oltvai ZN, Milliman CL and Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609–619

    Article  CAS  Google Scholar 

  • Omura GA, Brady MF, Homesley HD, Yordan E, Major FJ, Buchsbaum HJ and Park RC (1991) Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J Clin Oncol 9: 1138–1150

    Article  CAS  Google Scholar 

  • Owen-Schaub LB, Radinsky R, Kruzel E, Berry K and Yonehara S (1994) Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res 54: 1580–1586

    CAS  PubMed  Google Scholar 

  • Pezella F, Turley H, Kuzu I, Tungekar MF, Dunnill MS, Pierce CB, Harris A, Gatter KC and Mason DY (1993) Bcl-2 protein in non-small cell lung carcinoma. N Engl J Med 329: 690–694

    Article  Google Scholar 

  • Rodenburg CJ, Cornelisse CJ, Heintz PAM, Hermans JO and Fleuren GJ (1987) Tumor ploidy as a major prognostic factor in advanced ovarian cancer. Cancer 59: 317–323

    Article  CAS  Google Scholar 

  • Shima Y, Nishimoto N, Ogata A, Fujii Y, Yoshizaki K and Kishimoto T (1995) Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood 85: 757–764

    CAS  PubMed  Google Scholar 

  • Shiraki K, Tsuji N, Shioda T, Isselbacher KJ and Takahashi H (1997) Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci USA 94: 6420–6425

    Article  CAS  Google Scholar 

  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A and Press MF (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707–712

    Article  CAS  Google Scholar 

  • Strand S, Hofmann WJ, Hug H, Müller M, Otto G, Strand D, Mariani SM, Stremmel W, Krammer PH and Galle PR (1996) Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells – a mechanism of immune evasion?. Nature Med 2: 1361–1366

    Article  CAS  Google Scholar 

  • Takahashi T, Tanaka M, Inazawa J, Abe T, Suda T and Nagata S (1994) Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol 6: 1567–1574

    Article  CAS  Google Scholar 

  • Tanaka M, Suda T, Haze K, Nakamura N, Sato K, Kimura F, Motoyoshi K, Mizuki M, Tagawa S, Ohga S, Hatake K, Drummond AH and Nagata S (1996) Fas ligand in human serum. Nat Med 2: 317–322

    Article  CAS  Google Scholar 

  • Ungefroren H, Voss M, Jansen M, Roeder C, Henne-Bruns D, Kremer B and Kalthoff H (1998) Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. Cancer Res 58: 1741–1749

    CAS  PubMed  Google Scholar 

  • Wakahara Y, Nawa A, Okamoto T, Hayakawa A, Kikkawa F, Suganuma N, Wakahara F and Tomoda Y (1997) Combination effect of anti-Fas antibody and chemotherapeutic drugs in ovarian cancer cells in vitro. Oncology 54: 48–54

    Article  CAS  Google Scholar 

  • Wehrli BM, Krajewski S, Gascoyne RD, Reed JC and Gilks CB (1998) Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in ovarian surface epithelial tumors. Int J Gynecol Pathol 17: 255–260

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    S Munakata, H Miwa, H Kanno & K Aozasa

  2. Department of Obstetrics and Gynecology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    T Enomoto

  3. Department of Pathology, Osaka Police Hospital, 10-31 Kitayamacho, Tennoji-ku, Osaka, 543-0035, Japan

    M Tsujimoto

  4. Department of Obstetrics and Gynecology, Osaka Police Hospital, 10-31 Kitayamacho, Tennoji-ku, Osaka, 543-0035, Japan

    Y Otsuki

Authors
  1. S Munakata
    View author publications

    Search author on:PubMed Google Scholar

  2. T Enomoto
    View author publications

    Search author on:PubMed Google Scholar

  3. M Tsujimoto
    View author publications

    Search author on:PubMed Google Scholar

  4. Y Otsuki
    View author publications

    Search author on:PubMed Google Scholar

  5. H Miwa
    View author publications

    Search author on:PubMed Google Scholar

  6. H Kanno
    View author publications

    Search author on:PubMed Google Scholar

  7. K Aozasa
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Munakata, S., Enomoto, T., Tsujimoto, M. et al. Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms. Br J Cancer 82, 1446–1452 (2000). https://doi.org/10.1054/bjoc.1999.1073

Download citation

  • Received: 20 April 1999

  • Revised: 16 November 1999

  • Accepted: 24 November 1999

  • Published: 21 March 2000

  • Issue date: 01 April 2000

  • DOI: https://doi.org/10.1054/bjoc.1999.1073

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Fas ligand
  • CD95 ligand
  • bcl-2
  • epithelial ovarian neoplasms
  • immunohistochemistry
  • prognosis

This article is cited by

  • Candidate protein biomarkers in pancreatic neuroendocrine neoplasms grade 3

    • Abir Salwa Ali
    • Aurel Perren
    • Eva Tiensuu Janson

    Scientific Reports (2020)

  • The role of CD95 and CD95 ligand in cancer

    • M E Peter
    • A Hadji
    • P Ceppi

    Cell Death & Differentiation (2015)

  • Corticotropin-releasing hormone (CRH) is expressed in the human cervical carcinoma cells (HeLa) and upregulates the expression of Fas ligand

    • Eirini Taliouri
    • Thomas Vrekoussis
    • Antonis Makrigiannakis

    Tumor Biology (2013)

  • Weapons Ovarian Epithelial Tumors May Use in Immune Escape: An Immunohistochemical Correlational Study

    • Eiman Adel Hasby

    Pathology & Oncology Research (2012)

  • Differential expression of Fas family members and Bcl-2 family members in benign versus malignant epithelial ovarian cancer (EOC) in North Indian population

    • Parvesh Chaudhry
    • Radhika Srinivasan
    • Firuza D. Patel

    Molecular and Cellular Biochemistry (2012)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited