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Evaluation of HER-2 status in breast carcinoma by fluorescencein situ hybridization and immunohistochemistry

Abstract

Background

Evaluation of HER-2 status is essential for selecting appropriate candidates for treatment with trastuzumab, a recombinant humanized monoclonal antibody active against human epidermal growth factor receptor-2 (HER-2) protein.

Methods

To standardize a HER-2 diagnostic system for breast cancer tissue, we compared immunohistochemistry (IHC) and fluorescencein situ hybridization (FISH) results. We studied specimens from 110 patients with invasive ductal breast cancer who underwent operation. IHC analysis was performed using HercepTest™ (Dako A/S), and results assessed according to the HercepTest™ criteria. FISH was performed using a PathVysion™ HER-2 DNA probe kit (Vysis Inc.), with specimens considered HER-2 positive if the ratio of the total HER-2 signals to chromosome 17 centromere (CEP17) signals was greater than 2.

Results

FISH results were indefinite in 3 patients and positive in 24 patients (22%). IHC scores were 0 in 27 patients (25%), 1+in 53 patients (48%), 2+in 10 patients (9%), and 3+in 20 patients (18%). All 20 patients with a score of 3+by IHC were positive by FISH, with only 1 (10%) of 10 patients with an IHC score of 2+positive by FISH.

Conclusions

Our results indicated that an IHC score of 3+is equivalent to FISH-positivity for HER-2 diagnosis, while patients with an IHC score of 2+should undergo FISH testing.

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Abbreviations

HER-2:

Human epidermal growth factor receptor-2

FISH:

Fluorescencein situ hybridization

IHC:

Immunohistochemistry

CEP 17:

Chromosome 17 centromere

References

  1. 1)

    Yanden Y, Ullrich A: Growth factor receptor tyrosine kinases.Annu Rev Biochem 57: 443–478, 1988.

  2. 2)

    Coussens L, Yang-Feng TL, Liao Y-C, Chen E, Gray A, McGrath J, Seeburg TA, Libermann TA, Schlessinger J, Francke U, Levinson A, Ullrich A: Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.Science 230: 1132–1139, 1985.

  3. 3)

    Yamamoto T, Iwaki S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K: Similarity of protein encoded by human c-erb-B-2 gene to epidermal growth factor receptor.Nature 319: 230–234, 1986.

  4. 4)

    King CR, Kraus MH, Aaronson SA: Amplification of a novel v-erbB-related gene in a human mammary carcinoma.Science 229: 974–976, 1985.

  5. 5)

    Yokota J, Yamamoto T, Toyoshima K, Toyoshima K, Terada M, Sugimura T, Battifora H, Cline MJ: Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo.Lancet 1: 765–768, 1986.

  6. 6)

    Kern JA, Schwartz DA, Nordberg JE, Weiner DB, Greene MI, Torney L, Robinson R: pl85neu expression in human lung adenocarcinomas predicts shortened survival.Cancer Res 50: 5184–5191, 1990.

  7. 7)

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

  8. 8)

    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.Science 235: 177–182, 1987.

  9. 9)

    Wright C, Angus B, Nicholson S, Sainsbury JRC, Cairns J, Gullick WJ, Kelly P, Harris AL and Wilson Home CH: Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.Cancer Res 49: 2087–2090, 1989.

  10. 10

    Giai M, Roagna R, Ponzone R, Bortoli M, Dati C, Sismondi P: Prognostic and predictive relevance of c-erbB-2 andras expression in node positive and negative breast cancer.Anticancer Res 14: 1441–1450, 1994.

  11. 11

    Allred DC, Clark GM, Tandon AK, Molina R, Tormey DC, Osborne CK, Gilchrist KW, Mansour EG, Abeloff M, Eudey L, McGuire WL: HER-2/new in node-negative breast cancer: prognistic significance of overex-pression influenced by the presence of in situ carcinoma.J Clin Oncol 10: 599–605, 1992.

  12. 12

    Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, Fisher ER, Lippman ME, Wickerham DL, Wolmark N: erbB-2and responcse to Doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer.J Natl Cancer Inst 90: 1361–1370, 1998.

  13. 13

    Burstein HJ, Kuter I, Richardson PG, Campos SM, Parker LM, Matulonis UA, Harris L, Garber JE, Younger J, Bunnell CA, Shulman LN, Winer EP: Herceptin and vinorelbine for HER-2-positive metastatic breast cancer: a phase II study.Proc Am Soc Clin Oncol 19: 102a, 2000.

  14. 14

    Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.J Clin Oncol 17: 2639–2648, 1999.

  15. 15

    Press MF, Bernstein L, Thomas PA, Meisner LF, Zhou JY, Ma, Y, Hung G, Robinson RA, Harris C, El-Naggar A, Slamon DJ, Phillips RN, Ross JS, Wolman SR, Flom KJ: HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.J Clin Oncol 15: 2894–2904, 1997.

  16. 16

    Pauletti G, Godolphin W, Press MF, Slamon DJ: Detection and quantitation of RER-2/new gene amplification in human breast cancer archival material using fluorescencein situ hybridization.Oncogene 13: 63–72, 1996.

  17. 17

    Sais PE, Kotts CE, Vetterlein D, Shepard M, Wong WLT: ELISA for quantitation of the extracellular domain of pl85HER2 in biological fluids.J Immunol Methods 132: 73–80, 1990.

  18. 18

    Leitzel K, Teramoto Y, Sampson E, Mauceri J, Langton BC, Demers L, Podczaski E, Harvey H, Sham-baugh S, Volas G, Weaver S, Lipton A: Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a proportion of breast cancer patients.J Clin Oncol 10: 1436–1443, 1992.

  19. 19

    Hynes NE, Stern DF: The biology oferbB-2/neu/ HER-2 and its role in cancer.Biochem Biophs Acta 1198: 165–184, 1994.

  20. 20

    Press MF, Hung G, Godolphin W, Slamon DJ: Sensitivity of HER-2/neu antibodies in archival tissue samples: Potential source of error in immunohistochemical studies of oncogene expression.Cancer Res 54: 2771–2777, 1994.

  21. 21

    Tsuda H, Sasano H, Akiyama F, Kurosumi M, Hasegawa T, Osamura RY, Sakamoto G: Evaluation of interobserver agreement in scoring immunohisto-chemical results of HER-2/neu (c-erbB-2) expression detected by HercepTest, Nichirei polyclonal antiboby, CB11, and TAB250 in breast carcinoma.Pathol Int 52: 126–134, 2002.

  22. 22

    Mass RD, Press M, Anderson S, Murphy M, Slamon D: Improved survival benefit from Herceptin (trastuzumab) in patients selected by fluorescence in situ hybridization (FISH).Proc Am Soc Clin Oncol 20: 22a, 2001.

  23. 23

    Vogel CL, Cobleigh M, Tripathy D, Mass R, Murphy M, Stewart SJ: Superior outcomes with Herceptin (trastuzumab) (H) fluorescence in situ hybridization (FISH)-selected patients.Proc Am Soc Clin Oncol 20: 22a, 2001.

  24. 24

    Japanese Breast Cancer Society: The general rules for clinical and pathological recording of breast cancer.Jpn J Surg 19: 612–632, 1989.

  25. 25

    Hoarg, MP, Sahin AA, Ordonez NG, Sneige N: HER- 2/neu gene amplification compared with HER-2/neu protein overexpression and interobserver reproducibility in invasive breast carcinoma.Am J Clin Patol 113: 852–859, 2000.

  26. 26

    Hatanaka Y, Hashizume K, Kamihara Y, Itoh H, Tsuda H, Osamura RY, Tani Y: Quantitative immuno-histo-chemical evaluation of HER2/neu expression with HERcepTest™ in breast carcinoma by image analysis.Pathol Inter 51: 33–36, 2001.

  27. 27

    Pauletti G, Dandekar S, Rong H, Ramos L, Peng H, Seshadri R, Slamon DJ: Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry.J Clin Oncol 18: 3651–3664, 2000.

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Author information

Correspondence to Hiroyuki Ogura or Futoshi Akiyama or Fujio Kasumi or Teruhisa Kazui or Goi Sakamoto.

Additional information

Reprint requests to Hiroyuki Ogura, Department of Breast Pathology, The Cancer Institute of the Japanese Foundation for Cancer Research, 1-37-1, Kami-lkebukuro, Toshima-ku, Tokyo 170-8455, Japan.

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Cite this article

Ogura, H., Akiyama, F., Kasumi, F. et al. Evaluation of HER-2 status in breast carcinoma by fluorescencein situ hybridization and immunohistochemistry. Breast Cancer 10, 234–240 (2003). https://doi.org/10.1007/BF02966723

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Key words

  • Breast cancer
  • HER-2
  • Fluorescencein situ hybridization
  • Immunohistochemistry