Skip to main content

Advertisement

SpringerLink
Log in

Immunohistochemical profiles of brain metastases from breast cancer

  • Clinical study - patient study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The aim of present study is to explore the immunohistochemical profiles of brain metastases from breast cancer. We retrospectively performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2/neu), and cytokeratin (CK) 5/6 in 29 patients with resected tumor specimens of brain metastases. Immunohistochemical staining for ER, PgR and HER2/neu was performed in 24 patients with primary tumors. The positive frequency of immunohistochemical profiles of ER, PgR, HER2/neu, and CK5/6, in the brain metastases were 13.8%, 6.9%, 37.9%, and 24.1%, respectively. The immunohistochemical profiles including ER, PgR, and HER2/neu of the primary tumor and the brain metastasis differed in seven patients (29.2%, N = 7/24). Interestingly, the biological characteristics of brain metastasis sometimes changed which were represented by immunohistochemical staining. Therefore, the changes in the biological features of breast cancer should be taken into account when developing treatment strategies, including new molecular-targeted drugs, for brain metastases.

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

References

  1. Lin N, Bellon J, Winer E (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617. doi:10.1200/JCO.2004.01.175

    Article  PubMed  Google Scholar 

  2. Clayton AJ, Danson S, Jolly S et al (2004) Incidence of central metastasis in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639–643

    PubMed  CAS  Google Scholar 

  3. Gabos Z, Sinha R, Hanson J et al (2006) Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 24:5658–5663. doi:10.1200/JCO.2006.07.0250

    Article  PubMed  CAS  Google Scholar 

  4. Matsumoto K, Shimizu C, Fujiwara Y (2006) The next step to approaching central nervous system metastasis in HER-2-positive metastatic breast patients. Asia Pac J Clin Oncol 2:6–8. doi:10.1111/j.1743-7563.2006.00044.x

    Article  Google Scholar 

  5. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of HER2/neu oncogene. Science 235:177–182. doi:10.1126/science.3798106

    Article  PubMed  CAS  Google Scholar 

  6. Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792. doi:10.1056/NEJM200103153441101

    Article  PubMed  CAS  Google Scholar 

  7. Piccart-Gebhart MJ, Proctor M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672. doi:10.1056/NEJMoa052306

    Article  PubMed  CAS  Google Scholar 

  8. Pestalozzi BC, Brignoli S (2000) Trastuzumab in CSF. J Clin Oncol 18:2349–2351

    PubMed  CAS  Google Scholar 

  9. Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8:235–244. doi:10.1016/S1470-2045(07)70074-8

    Article  PubMed  Google Scholar 

  10. Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374. doi:10.1158/1078-0432.CCR-04-0220

    Article  PubMed  CAS  Google Scholar 

  11. Tham YL, Sexton K, Kramer R et al (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704. doi:10.1002/cncr.22041

    Article  PubMed  Google Scholar 

  12. Perren A, Weng L-P, Boag AH et al (1999) Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinoma of the breast. Am J Pathol 155:1254–1260

    Google Scholar 

  13. Harvey JM, Clark G, Ml Osborne CK et al (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-biding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17:1474–1481

    PubMed  CAS  Google Scholar 

  14. Shimizu C, Fukutomi T, Tsuda H et al (2000) c-erbB-2 Protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. J Surg Oncol 73:17–20. doi:10.1002/(SICI)1096-9098(200001)73:1<17::AID-JSO5>3.0.CO;2-2

    Article  PubMed  CAS  Google Scholar 

  15. Pertschuk LP, Axiotis CA, Feldman JG et al (1999) Marked intratumoral heterogeneity of the proto-oncogene Her-2/neu determined by three different detection systems. Breast J 5:369–374. doi:10.1046/j.1524-4741.1999.97088.x

    Article  PubMed  Google Scholar 

  16. Gong Y, Booser DJ, Sneige N (2005) Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer 103:1763–1769. doi:10.1002/cncr.20987

    Article  PubMed  CAS  Google Scholar 

  17. Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M et al (2002) Comparison of HER2-status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 13:1036–1043. doi:10.1093/annonc/mdf252

    Article  PubMed  CAS  Google Scholar 

  18. Regitnig P, Schippinger W, Lindbauer M, Samonigg H, Lax SF (2004) Change of HER2/neu status in a subset of distant metastases from breast carcinomas. J Pathol 203:918–926. doi:10.1002/path.1592

    Article  PubMed  CAS  Google Scholar 

  19. Pectasides D, Gaglia A, Arapantoni-Dadioti P, Bobota A, Valavanis C, Kostopoulou V et al (2006) Her2/neu status of primary breast cancer and corresponding metastatic sites in patients with advanced breast cancer treated with trastuzumab-based therapy. Anticancer Res 26:647–654

    PubMed  CAS  Google Scholar 

  20. Lower EE, Glass E, Blau R, Harman S (2008) Her-2/neu expression in primary and metastatic breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-008-9931-6

    PubMed  Google Scholar 

  21. Zidan J, Dashkovsky I, Stayerman C, Basher W, Cozacov C, Hadary A (2005) Comparison of HER2/neu overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93:552–556. doi:10.1038/sj.bjc.6602738

    Article  PubMed  CAS  Google Scholar 

  22. Niehans GA, Singleton TP, Dykoski D, Kiang DT (1993) Stability of HER-2/neu expression over time and at multiple metastatic sites. J Natl Cancer Inst 85:1230–1235. doi:10.1093/jnci/85.15.1230

    Article  PubMed  CAS  Google Scholar 

  23. Cardoso F, Di Leo A, Larsimont D, Gancberg D, Rouas G, Dolce S et al (2001) Evaluation of HER2, p53, bcl-2, topoisomerase II-alfa, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes. Ann Oncol 12:615–620. doi:10.1023/A:1011182524684

    Article  PubMed  CAS  Google Scholar 

  24. Tsutsui S, Ohno S, Murakami S, Kataoka A, Kinoshita J, Hachitanda Y (2002) EGFR, c-erbB2, and p53 protein in the primary lesions and paired metastatic regional lymph nodes in breast cancer. EJSO 28:383–387. doi:10.1053/ejso.2002.1259

    Article  PubMed  CAS  Google Scholar 

  25. Lear-Kaul KC, Yoon HR, Kleinschmidt-DeMasters BK et al (2003) HER2/neu status in breast cancer metastases to the central nervous system. Arch Pathol Lab Med 127:1451–1457

    PubMed  CAS  Google Scholar 

  26. Kamby C, Rasmussen BB, Kristensen B (1989) Oestrogen receptor status of primary breast carcinomas and their metastases. Relation to pattern of spread and survival after recurrence. Br J Cancer 60:252–257

    PubMed  CAS  Google Scholar 

  27. Li BD, Byskosh A, Molteni A, Duda RB (1994) Estrogen and progesterone receptor concordance between primary and recurrent breast cancer. J Surg Oncol 57:71–77. doi:10.1002/jso.2930570202

    Article  PubMed  CAS  Google Scholar 

  28. Hicks DG, Short SM, Prescott NL et al (2006) Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol 30:1097–1104. doi:10.1097/01.pas.0000213306.05811.b9

    PubMed  Google Scholar 

  29. Mohsin SK, Weiss HL, Gonzarrez MC et al (2005) Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol 23:2460–2468. doi:10.1200/JCO.2005.00.661

    Article  PubMed  CAS  Google Scholar 

  30. Nagata Y, Lan LH, Zhou X et al (2004) PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6:117–127. doi:10.1016/j.ccr.2004.06.022

    Article  PubMed  CAS  Google Scholar 

  31. Nahta R, Yu D, Hung MC et al (2006) Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 3:269–280. doi:10.1038/ncponc0509

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Ministry of Health, Labour, and Welfare. The authors thank Kunihiko Seki, M.D. (Clinical Laboratory Division, National Cancer Center Hospital), Eriko Nakano, M.D., Mayu Yunokawa, M.D., Tsutomu Kouno, M.D., Masashi Ando, M.D., Noriyuki Katsumata, M.D., and Kenji Tamura, M.D., PhD. (Breast and Medical Oncology Division, National Cancer Center Hospital) for their assistance.

Author information

Authors and Affiliations

  1. Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Kan Yonemori, Chikako Shimizu, Makiko Ono & Yasuhiro Fujiwara

  2. Clinical Laboratory Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Koji Tsuta & Yasuhiro Fujiwara

  3. Dako Japan Inc., 2-5-1, Kouraku, Bunkyo-ku, Tokyo, 112-0004, Japan

    Yutaka Hatanaka & Kaoru Hashizume

  4. Pathology Division, National Cancer Center Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yukihiro Nakanishi

  5. Department of Surgical Pathology, Sapporo Medical School of Medicine, South 1 West 16, Chuo-ku, Sapporo, Hokkaido, 104-0045, Japan

    Tadashi Hasegawa

  6. Neurosurgery Division, National Cancer Center Hospital, Tokyo, Japan

    Yasuji Miyakita, Yoshitaka Narita & Soichiro Shibui

Authors
  1. Kan Yonemori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koji Tsuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chikako Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yutaka Hatanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kaoru Hashizume
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Makiko Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yukihiro Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tadashi Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yasuji Miyakita
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoshitaka Narita
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Soichiro Shibui
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yasuhiro Fujiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Koji Tsuta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yonemori, K., Tsuta, K., Shimizu, C. et al. Immunohistochemical profiles of brain metastases from breast cancer. J Neurooncol 90, 223–228 (2008). https://doi.org/10.1007/s11060-008-9654-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-008-9654-x

Keywords

Search

Navigation