Skip to main content
SpringerLink
Log in

Gamma-glutamyl transpeptidase immunoreactivity in benign and malignant breast tissue

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

GGT 129, a polyclonal antibody directed against gamma-glutamyltranspeptidase (GGT), was used to study GGT expression in formalin-fixedparaffin-embedded tissues from normal breast, 24 benign lesions, 27 in situcarcinomas or atypical hyperplasias, and 79 infiltrating mammary carcinomas.Epithelium of the ducts and ductules in normal breast tissue showedimmunoreactivity along the apical surface. There was a strong correlation (P< 0.01) between the histologic classification of the tissue and GGTexpression. All of the benign breast lesions stained positive for GGT. Amongin situ carcinomas and atypical hyperplasias, 5/27 (19%) werenegative for GGT while 22/27 were immunopositive. Infiltrating carcinomasshowed the greatest deviation from normal tissue with 23/79 (29%)negative for GGT. GGT expression in benign and malignant breast tissue wasnot correlated with the age of the patient, suggesting that menopausalstatus does not influence expression of GGT. Correlation of GGTimmunoreactivity with tubule formation, nuclear pleomorphism, mitoses,grade, size of tumor, lymph node status, and ER/PR status was performed for69 cases of infiltrating ductal adenocarcinoma. There were no statisticallysignificant relationships between the level of GGT immunoreactivity and anyof the parameters. The loss of GGT in some of the cases is evidence thatthis enzyme is not required for mammary tumor development or maintenance.However, as GGT is a component of the pathways that metabolize glutathioneand glutathione-conjugates, the difference in levels of the enzyme ininvasive breast cancers may be one explanation for the variation inchemotherapy response that has been observed in patients treated foradvanced mammary cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Chapter © 2017

References

  1. Boring CC, Squires TS, Tong T: Cancer statistics, 1991. CA-Cancer J Clin 41: 19–36, 1991

    Google Scholar 

  2. Hanigan MH, Ricketts WA: Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. Biochemistry 32: 6302–6306, 1993

    Google Scholar 

  3. Hanigan MH, Frierson HF Jr: Immunohistochemical detection of gamma-glutamyl transpeptidase in normal human tissue. J Histochem Cytochem 44: 1101–1108, 1996

    Google Scholar 

  4. El-akawi Z, Abu-hadid M, Perez R, Glavy J, Zdanowicz J, Creaven PJ, Pendyala L: Altered glutathione metabolism in oxaliplatin resistant ovarian carcinoma cell. Cancer Lett 105: 5–14, 1996

    Google Scholar 

  5. Ahmad S, Okine L, Wood R, Aljian J, Vistica DT: Gammaglutamyltranspeptidase and maintenance of thiol pools in tumor cells resistant to alkylating agents. J Cell Physiol 131: 240–246, 1987

    Google Scholar 

  6. Lewis AL, Hayes JD, Wolf CR: Glutathione and glutathione-dependent enzymes in ovarian adenocarcinoma cell lines derived from a patient before and after the onset of drug resistance: intrinsic differences and cell cycle effects. Carcinogenesis 9: 1283–1287, 1988

    Google Scholar 

  7. Lau HM, Lewis AD, Ehsan MN, Sikic BI: Multifactorial mechanisms associated with broad cross-resistance of ovarian carcinoma cells selected by cyanomorpholino doxorubicin. Cancer Res 51: 5181–5187, 1991

    Google Scholar 

  8. Godwin AK, Meister A, O'Dwyer PJ, Huang CS, Hamilton TC, Anderson ME: High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci USA 89: 3070–3074, 1992

    Google Scholar 

  9. Fiala S, Trout EC Jr, Teague CA, Fiala ES: Gamma-glutamyltransferase, a common marker of human epithelial tumors. Cancer Detection and Prevention 3: 471–485, 1980

    Google Scholar 

  10. Hanigan MH, Frierson HF Jr, Brown JE, Lovell MA, Taylor PT: Human ovarian tumors express gamma-glutamyl transpeptidase. Cancer Res 54: 286–290, 1994

    Google Scholar 

  11. Gerber MA, Thung SN: Enzyme patterns in human hepatocellular carcinoma. Am J Pathol 98: 395–400, 1980

    Google Scholar 

  12. Dempo K, Elliot KAC, Desmond W, Fishman WH: Demonstration of gamma-glutamyl transferase, alkaline phosphatase, CEA and HCG in human lung cancer. Oncodev Biol Med 2: 21–37, 1981

    Google Scholar 

  13. Levine SE, Budwit DA, Michalopoulos GK, Georgiade GS, McCarty KS Jr: Gamma-glutamyl transpeptidase activity in benign and malignant human mammary epithelial lesions. Arch Pathol Lab Med 107: 423–427, 1983

    Google Scholar 

  14. Bard S, Noel P, Chauvin F, Quash G: Gamma-glutamyl transpeptidase activity in human breast lesions: an unfavorable prognostic sign. Brit J Cancer 53: 637–642, 1986

    Google Scholar 

  15. Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow up. Histopathology 19: 403–410, 1991

    Google Scholar 

  16. Dawson J, Smith GD, Boak J, Peters TJ: Gamma-glutamyl-transferase in human and mouse breast tumors. Clin Chim Acta 96: 37–42, 1979

    Google Scholar 

  17. Neuwald PD, Anderson C, Salivar WO, Aldenderfer PH, Dermody WC et al.: Expression of oncodevelopmental gene products by human tumor cells in culture. JNCI 64: 447–459, 1980

    Google Scholar 

  18. Fisher ER, Gregorio RM, Fisher B: The pathology of invasive breast cancer: a syllabus from findings of the national surgical adjuvant breast project (Project No. 4). Cancer 36: 1–84, 1975

    Google Scholar 

  19. Horiuchi S, Inoue M, Morino Y: Gamma-glutamyl transpeptidase sidedness of its active site on renal brush border membrane. Eur J Biochem 87: 429–437, 1978

    Google Scholar 

  20. Meredith MJ, Williams GM: Intracellular glutathione cycling by γ-glutamyl transpeptidase in tumorigenic and non-tumorigenic cultured rat liver cells. J Biol Chem 261: 4986–4992, 1986

    Google Scholar 

  21. Perry RR, Levin M, Barranco SC: Glutathione levels and variability in breast tumors and normal tissue. Cancer 72: 783–787, 1993

    Google Scholar 

  22. Friedman HS, Colvin OM, Kaufmann SH, Ludeman SM, Bullock N, Bigner DD, Griffith OW: Cyclophosphamide resistance in medulloblastoma. Cancer Res 52: 5373–5378, 1992

    Google Scholar 

  23. Canada A, Herman L, Kidd K, Robertson C, Trump D: Glutathione depletion increases the cytotoxicity of melphalan to PC-3, an androgen-insensitive prostate cancer cell line. Cancer Chemother Pharmacol 32: 73–77, 1993

    Google Scholar 

  24. Hanigan MH: Expression of gamma-glutamyl transpeptidase provides tumor cells with a selective growth advantage at physiologic concentrations of cyst(e)ine. Carcinogenesis 16: 181–185, 1995

    Google Scholar 

  25. Bailey HH, Gipp JJ, Mulcahy RT: Increased expression of gamma-glutamyl transpeptidase in transfected tumor cells and its relationship to drug sensitivyt. Cancer Lett 87: 163–170, 1994

    Google Scholar 

  26. Hochwald SN, Harrison LE, Rose DM, Anderson M, Burt ME: Gamma-glutamyl transpeptidase mediation of tumor glutathione untilization in vivo. JNCI 88: 193–197, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia, 22908, USA

    Janet R. Durham & Henry F. Frierson Jr

  2. Departments of Cell Biology and Obstetrics and Gynecology, University of Virginia Health Sciences Center, Charlottesville, Virginia, 22908, USA

    Marie H. Hanigan

Authors
  1. Janet R. Durham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry F. Frierson Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marie H. Hanigan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Durham, J.R., Frierson, H.F. & Hanigan, M.H. Gamma-glutamyl transpeptidase immunoreactivity in benign and malignant breast tissue. Breast Cancer Res Treat 45, 55–62 (1997). https://doi.org/10.1023/A:1005889006557

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005889006557

Search

Navigation