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. 1995 May;48(5):429–432. doi: 10.1136/jcp.48.5.429

Immunohistochemical quantitation of oestrogen receptors and proliferative activity in oestrogen receptor positive breast cancer.

V Jensen 1, M Ladekarl 1
PMCID: PMC502618  PMID: 7629289

Abstract

AIM--To evaluate the effect of the duration of formalin fixation and of tumour heterogeneity on quantitative estimates of oestrogen receptor content (oestrogen receptor index) and proliferative activity (MIB-1 index) in breast cancer. METHODS--Two monoclonal antibodies, MIB-1 and oestrogen receptor, were applied to formalin fixed, paraffin wax embedded tissue from 25 prospectively collected oestrogen receptor positive breast carcinomas, using a microwave antigen retrieval method. Tumour tissue was allocated systematically to different periods of fixation to ensure minimal intraspecimen variation. The percentages of MIB-1 positive and oestrogen receptor positive nuclei were estimated in fields of vision sampled systematically from the entire specimen and from the whole tumour area of one "representative" cross-section. RESULTS--No correlation was found between the oestrogen receptor and MIB-1 indices and the duration of formalin fixation. The estimated MIB-1 and oestrogen receptor indices in tissue sampled systematically from the entire tumour were closely correlated with estimates obtained in a "representative" section. The intra- and interobserver correlation of the MIB-1 index was good, although a slight systematical error at the second assessment of the intraobserver study was noted. CONCLUSION--Quantitative estimates of oestrogen receptor content and proliferative activity are not significantly influenced by the period of fixation in formalin, varying from less than four hours to more than 48 hours. The MIB-1 and the oestrogen receptor indices obtained in a "representative" section do not deviate significantly from average indices determined in tissue samples from the entire tumour. Finally, the estimation of MIB-1 index is reproducible, justifying its routine use.

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Selected References

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  1. Aaltomaa S., Lipponen P., Eskelinen M., Kosma V. M., Marin S., Alhava E., Syrjänen K. Hormone receptors as prognostic factors in female breast cancer. Ann Med. 1991 Dec;23(6):643–648. doi: 10.3109/07853899109148097. [DOI] [PubMed] [Google Scholar]
  2. Andersen J., Orntoft T. F., Poulsen H. S. Immunohistochemical demonstration of estrogen receptors (ER) in formalin-fixed, paraffin-embedded human breast cancer tissue by use of a monoclonal antibody to ER. J Histochem Cytochem. 1988 Dec;36(12):1553–1560. doi: 10.1177/36.12.2461414. [DOI] [PubMed] [Google Scholar]
  3. Andersen J., Poulsen H. S. Immunohistochemical analysis of estrogen receptors (ER) using formalin-fixed paraffin-embedded breast cancer tissue: correlation with clinical endocrine response. J Steroid Biochem. 1988;30(1-6):337–339. doi: 10.1016/0022-4731(88)90119-7. [DOI] [PubMed] [Google Scholar]
  4. Andersen J., Thorpe S. M., King W. J., Rose C., Christensen I., Rasmussen B. B., Poulsen H. S. The prognostic value of immunohistochemical estrogen receptor analysis in paraffin-embedded and frozen sections versus that of steroid-binding assays. Eur J Cancer. 1990 Apr;26(4):442–449. doi: 10.1016/0277-5379(90)90013-j. [DOI] [PubMed] [Google Scholar]
  5. Bacus S. S., Goldschmidt R., Chin D., Moran G., Weinberg D., Bacus J. W. Biological grading of breast cancer using antibodies to proliferating cells and other markers. Am J Pathol. 1989 Nov;135(5):783–792. [PMC free article] [PubMed] [Google Scholar]
  6. Barnard N. J., Hall P. A., Lemoine N. R., Kadar N. Proliferative index in breast carcinoma determined in situ by Ki67 immunostaining and its relationship to clinical and pathological variables. J Pathol. 1987 Aug;152(4):287–295. doi: 10.1002/path.1711520407. [DOI] [PubMed] [Google Scholar]
  7. Cattoretti G., Becker M. H., Key G., Duchrow M., Schlüter C., Galle J., Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992 Dec;168(4):357–363. doi: 10.1002/path.1711680404. [DOI] [PubMed] [Google Scholar]
  8. Esteban J. M., Kandalaft P. L., Mehta P., Odom-Maryon T. L., Bacus S., Battifora H. Improvement of the quantification of estrogen and progesterone receptors in paraffin-embedded tumors by image analysis. Am J Clin Pathol. 1993 Jan;99(1):32–38. doi: 10.1093/ajcp/99.1.32. [DOI] [PubMed] [Google Scholar]
  9. Gerdes J., Lelle R. J., Pickartz H., Heidenreich W., Schwarting R., Kurtsiefer L., Stauch G., Stein H. Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. J Clin Pathol. 1986 Sep;39(9):977–980. doi: 10.1136/jcp.39.9.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gundersen H. J., Jensen E. B. The efficiency of systematic sampling in stereology and its prediction. J Microsc. 1987 Sep;147(Pt 3):229–263. doi: 10.1111/j.1365-2818.1987.tb02837.x. [DOI] [PubMed] [Google Scholar]
  11. Hall P. A., Levison D. A., Woods A. L., Yu C. C., Kellock D. B., Watkins J. A., Barnes D. M., Gillett C. E., Camplejohn R., Dover R. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol. 1990 Dec;162(4):285–294. doi: 10.1002/path.1711620403. [DOI] [PubMed] [Google Scholar]
  12. Helin M. L., Helle M. J., Helin H. J., Isola J. J. Proliferative activity and steroid receptors determined by immunohistochemistry in adjacent frozen sections of 102 breast carcinomas. Arch Pathol Lab Med. 1989 Aug;113(8):854–857. [PubMed] [Google Scholar]
  13. Key G., Becker M. H., Baron B., Duchrow M., Schlüter C., Flad H. D., Gerdes J. New Ki-67-equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest. 1993 Jun;68(6):629–636. [PubMed] [Google Scholar]
  14. Ladekarl M. The influence of tissue processing on quantitative histopathology in breast cancer. J Microsc. 1994 May;174(Pt 2):93–100. doi: 10.1111/j.1365-2818.1994.tb03453.x. [DOI] [PubMed] [Google Scholar]
  15. McCarty K. S., Jr, Miller L. S., Cox E. B., Konrath J., McCarty K. S., Sr Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985 Aug;109(8):716–721. [PubMed] [Google Scholar]
  16. McCarty K. S., Jr, Szabo E., Flowers J. L., Cox E. B., Leight G. S., Miller L., Konrath J., Soper J. T., Budwit D. A., Creasman W. T. Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 1986 Aug;46(8 Suppl):4244s–4248s. [PubMed] [Google Scholar]
  17. McCormick D., Yu C., Hobbs C., Hall P. A. The relevance of antibody concentration to the immunohistological quantification of cell proliferation-associated antigens. Histopathology. 1993 Jun;22(6):543–547. doi: 10.1111/j.1365-2559.1993.tb00174.x. [DOI] [PubMed] [Google Scholar]
  18. Sampson S. A., Kreipe H., Gillett C. E., Smith P., Chaudary M. A., Khan A., Wicks K., Parwaresch R., Barnes D. M. KiS1--a novel monoclonal antibody which recognizes proliferating cells: evaluation of its relationship to prognosis in mammary carcinoma. J Pathol. 1992 Oct;168(2):179–185. doi: 10.1002/path.1711680205. [DOI] [PubMed] [Google Scholar]
  19. Siitonen S. M., Isola J. J., Rantala I. S., Helin H. J. Intratumor variation in cell proliferation in breast carcinoma as determined by antiproliferating cell nuclear antigen monoclonal antibody and automated image analysis. Am J Clin Pathol. 1993 Mar;99(3):226–231. doi: 10.1093/ajcp/99.3.226. [DOI] [PubMed] [Google Scholar]
  20. Tahan S. R., Neuberg D. S., Dieffenbach A., Yacoub L. Prediction of early relapse and shortened survival in patients with breast cancer by proliferating cell nuclear antigen score. Cancer. 1993 Jun 1;71(11):3552–3559. doi: 10.1002/1097-0142(19930601)71:11<3552::aid-cncr2820711115>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  21. Verhoeven D., Bourgeois N., Derde M. P., Kaufman L., Buyssens N. Comparison of cell growth in different parts of breast cancers. Histopathology. 1990 Dec;17(6):505–509. doi: 10.1111/j.1365-2559.1990.tb00789.x. [DOI] [PubMed] [Google Scholar]
  22. Veronese S. M., Gambacorta M., Gottardi O., Scanzi F., Ferrari M., Lampertico P. Proliferation index as a prognostic marker in breast cancer. Cancer. 1993 Jun 15;71(12):3926–3931. doi: 10.1002/1097-0142(19930615)71:12<3926::aid-cncr2820711221>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  23. Wintzer H. O., Zipfel I., Schulte-Mönting J., Hellerich U., von Kleist S. Ki-67 immunostaining in human breast tumors and its relationship to prognosis. Cancer. 1991 Jan 15;67(2):421–428. doi: 10.1002/1097-0142(19910115)67:2<421::aid-cncr2820670217>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]

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