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. 2001 Mar;84(6):783–790. doi: 10.1054/bjoc.2000.1672

Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas

F Fina 1, S Romain 1, L'H Ouafik 1, J Palmari 1, F Ben Ayed 2, S Benharkat 3, P Bonnier 4, F Spyratos 5, J A Foekens 6, C Rose 7, M Buisson 8, H Gérard 1, M O Reymond 1, J M Seigneurin 8, P M Martin 1
PMCID: PMC2363823  PMID: 11259092

Abstract

Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a35S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.com

Keywords: breast cancer, Epstein–Barr virus, polymerase chain reaction, real-time quantitative polymerase chain reaction, genotyping, in situ hybridization, laser capture microdissection

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Footnotes

Part of this work was presented to the VII Symposium of the International Association for Research on Epstein–Barr Virus and Associated Diseases, Hong-Kong, 13–16 November 1996.

On behalf of: K Rahal, A Gammoudi (Institut Salah Azaïz, Tunis, Tunisia); S Haddad, A Djemaa (Centre Hospitalier Universitaire, Constantine, Algeria); L Piana (Hôpital de la Conception, Marseille, France); JM Brandone, C Bressac (Clinique Bouchard, Marseille, France); C Charpin (Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine Nord, Marseille, France); M Pizzi-Anselme, J Del Grande, J Guidon (Laboratoire d'Anatomie Pathologique et Cytologie, Marseille, France); and the clinicians and pathologists from Centre René Huguenin (St Cloud, France); Dr Daniel den Hoed Cancer Center (Rotterdam, the Netherlands); and the Finsen Institute (Copenhagen, Denmark) who actively participated in the study.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen K. W., Mouridsen H. T., Castberg T., Fischerman K., Andersen J., Hou-Jensen K., Brincker H., Johansen H., Henriksen E., Rørth M. Organisation of the Danish adjuvant trials in breast cancer. Dan Med Bull. 1981 Aug;28(3):102–106. [PubMed] [Google Scholar]
  2. Bonnet M., Guinebretiere J. M., Kremmer E., Grunewald V., Benhamou E., Contesso G., Joab I. Detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst. 1999 Aug 18;91(16):1376–1381. doi: 10.1093/jnci/91.16.1376. [DOI] [PubMed] [Google Scholar]
  3. Bouchardy C., Parkin D. M., Wanner P., Khlat M. Cancer mortality among north African migrants in France. Int J Epidemiol. 1996 Feb;25(1):5–13. doi: 10.1093/ije/25.1.5. [DOI] [PubMed] [Google Scholar]
  4. Brink A. A., van Den Brule A. J., van Diest P., Meijer C. J. Re: detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst. 2000 Apr 19;92(8):655–656. doi: 10.1093/jnci/92.8.655. [DOI] [PubMed] [Google Scholar]
  5. Buisson M., Morand P., Genoulaz O., Bourgeat M. J., Micoud M., Seigneurin J. M. Changes in the dominant Epstein-Barr virus type during human immunodeficiency virus infection. J Gen Virol. 1994 Feb;75(Pt 2):431–437. doi: 10.1099/0022-1317-75-2-431. [DOI] [PubMed] [Google Scholar]
  6. Bustin S. A. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000 Oct;25(2):169–193. doi: 10.1677/jme.0.0250169. [DOI] [PubMed] [Google Scholar]
  7. Chang K. L., Chen Y. Y., Shibata D., Weiss L. M. Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues. Diagn Mol Pathol. 1992 Dec;1(4):246–255. [PubMed] [Google Scholar]
  8. Gaffey M. J., Frierson H. F., Jr, Mills S. E., Boyd J. C., Zarbo R. J., Simpson J. F., Gross L. K., Weiss L. M. Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol. 1993 Nov;6(6):721–728. [PubMed] [Google Scholar]
  9. Glaser S. L., Ambinder R. F., DiGiuseppe J. A., Horn-Ross P. L., Hsu J. L. Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int J Cancer. 1998 Feb 9;75(4):555–558. doi: 10.1002/(sici)1097-0215(19980209)75:4<555::aid-ijc10>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  10. Horiuchi K., Mishima K., Ohsawa M., Aozasa K. Carcinoma of stomach and breast with lymphoid stroma: localisation of Epstein-Barr virus. J Clin Pathol. 1994 Jun;47(6):538–540. doi: 10.1136/jcp.47.6.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jeannel D., Ghnassia M., Hubert A., Sancho-Garnier H., Eschwège F., Crognier E., de-Thé G. Increased risk of nasopharyngeal carcinoma among males of French origin born in Maghreb (north Africa). Int J Cancer. 1993 Jun 19;54(4):536–539. doi: 10.1002/ijc.2910540403. [DOI] [PubMed] [Google Scholar]
  12. Labrecque L. G., Barnes D. M., Fentiman I. S., Griffin B. E. Epstein-Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res. 1995 Jan 1;55(1):39–45. [PubMed] [Google Scholar]
  13. Lespagnard L., Cochaux P., Larsimont D., Degeyter M., Velu T., Heimann R. Absence of Epstein-Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction. Am J Clin Pathol. 1995 Apr;103(4):449–452. doi: 10.1093/ajcp/103.4.449. [DOI] [PubMed] [Google Scholar]
  14. Ouafik L., May V., Keutmann H. T., Eipper B. A. Developmental regulation of peptidylglycine alpha-amidating monooxygenase (PAM) in rat heart atrium and ventricle. Tissue-specific changes in distribution of PAM activity, mRNA levels, and protein forms. J Biol Chem. 1989 Apr 5;264(10):5839–5845. [PubMed] [Google Scholar]
  15. Ouafik L., May V., Saffen D. W., Eipper B. A. Thyroid hormone regulation of peptidylglycine alpha-amidating monooxygenase expression in anterior pituitary gland. Mol Endocrinol. 1990 Oct;4(10):1497–1505. doi: 10.1210/mend-4-10-1497. [DOI] [PubMed] [Google Scholar]
  16. Parkin D. M., Iscovich J. Risk of cancer in migrants and their descendants in Israel: II. Carcinomas and germ-cell tumours. Int J Cancer. 1997 Mar 17;70(6):654–660. doi: 10.1002/(sici)1097-0215(19970317)70:6<654::aid-ijc5>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  17. Penault-Llorca F., Adelaïde J., Houvenaeghel G., Hassoun J., Birnbaum D., Jacquemier J. Optimization of immunohistochemical detection of ERBB2 in human breast cancer: impact of fixation. J Pathol. 1994 May;173(1):65–75. doi: 10.1002/path.1711730111. [DOI] [PubMed] [Google Scholar]
  18. Rickinson A. B., Young L. S., Rowe M. Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells. J Virol. 1987 May;61(5):1310–1317. doi: 10.1128/jvi.61.5.1310-1317.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Romain S., Martin P. M., Klijn J. G., van Putten W. L., Look M. P., Guirou O., Foekens J. A. DNA-synthesis enzyme activity: a biological tool useful for predicting anti-metabolic drug sensitivity in breast cancer? Int J Cancer. 1997 Apr 22;74(2):156–161. doi: 10.1002/(sici)1097-0215(19970422)74:2<156::aid-ijc3>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  20. Steinitz R., Iscovich J. M., Katz L. Cancer incidence in young offspring of Jewish immigrants to Israel. A methodological study. I. Nasopharyngeal malignancies and Ewing sarcoma. Cancer Detect Prev. 1990;14(5):547–553. [PubMed] [Google Scholar]
  21. Tabbane F., Muenz L., Jaziri M., Cammoun M., Belhassen S., Mourali N. Clinical and prognostic features of a rapidly progressing breast cancer in Tunisia. Cancer. 1977 Jul;40(1):376–382. doi: 10.1002/1097-0142(197707)40:1<376::aid-cncr2820400153>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  22. Tabbane F., el May A., Hachiche M., Bahi J., Jaziri M., Cammoun M., Mourali N. Breast cancer in women under 30 years of age. Breast Cancer Res Treat. 1985;6(2):137–144. doi: 10.1007/BF02235745. [DOI] [PubMed] [Google Scholar]
  23. zur Hausen H. Viruses in human cancers. Science. 1991 Nov 22;254(5035):1167–1173. doi: 10.1126/science.1659743. [DOI] [PubMed] [Google Scholar]

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