Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Sep;72(3):732–737. doi: 10.1038/bjc.1995.402

Are fine-needle breast aspirates representative of the underlying solid tumour? A comparison of receptor levels, ploidy and the influence of cytokeratin gates.

I Brotherick 1, B K Shenton 1, T W Lennard 1
PMCID: PMC2033883  PMID: 7545418

Abstract

Fifty-three solid and 33 fine-needle aspirate (FNA) samples (20 paired) of human breast carcinomas were examined by flow cytometry. Experiments were conducted to assess whether FNA samples were phenotypically representative of the solid tumour. Quantification of oestrogen receptor (ER), epidermal growth factor receptor (EGFR), c-erbB-2 receptor levels and ploidy were examined on the total and cytokeratin-positive cell populations. The absolute number of molecules of cytokeratin per cell expressed on the FNA (n = 33) and solid tumour (n = 53) samples showed no significant difference, but, on a proportional basis, there was a significant difference between the two samples (P = 0.004), with lower expression exhibited by the FNAs. Examination of paired data showed no significant difference in the percentage of cytokeratin-positive cells (P = 0.51) or in the number of cytokeratin molecules expressed (P = 0.25). While the correlation for ER expression between paired tumour and FNA samples in the absence of cytokeratin gating was P = 0.06, r2 = 0.18, clear correlation was shown when a cytokeratin gate was used (P = 0.005, r2 = 0.4). Repeating this experiment for EGFR, it was found that no correlation was seen between FNA and solid tumour (P = 0.2, r2 = 0.14) in ungated populations, but use of the cytokeratin gate improved the correlation (P = 0.05, r2 = 0.3). A similar finding was seen with c-erbB-2 expression (P = 0.2, r2 = 0.1) without cytokeratin gating and when it was employed (P = 0.05, r2 = 0.4). Ploidy data showed concordance in 18/20 cases. Three cases of aneuploidy were missed by FNA, and this was because of an insufficient number of cells for analysis. The presented data suggest that FNAs are representative of solid tumours and may be useful for measuring receptor levels on clinical material when cytokeratin gating is used. However, observation by light microscopy is still necessary to confirm the presence of tumour cells in FNAs subjected to flow cytometry.

Full text

PDF
732

Selected References

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

  1. Angus B., Purvis J., Stock D., Westley B. R., Samson A. C., Routledge E. G., Carpenter F. H., Horne C. H. NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue. J Pathol. 1987 Dec;153(4):377–384. doi: 10.1002/path.1711530411. [DOI] [PubMed] [Google Scholar]
  2. Brockhoff G., Hofstaedter F., Knuechel R. Flow cytometric detection and quantitation of the epidermal growth factor receptor in comparison to Scatchard analysis in human bladder carcinoma cell lines. Cytometry. 1994 Sep 1;17(1):75–83. doi: 10.1002/cyto.990170110. [DOI] [PubMed] [Google Scholar]
  3. Brotherick I., Lennard T. W., Cook S., Johnstone R., Angus B., Winthereik M. P., Shenton B. K. Use of the biotinylated antibody DAKO-ER 1D5 to measure oestrogen receptor on cytokeratin positive cells obtained from primary breast cancer cells. Cytometry. 1995 May 1;20(1):74–80. doi: 10.1002/cyto.990200111. [DOI] [PubMed] [Google Scholar]
  4. Brotherick I., Lennard T. W., Wilkinson S. E., Cook S., Angus B., Shenton B. K. Flow cytometric method for the measurement of epidermal growth factor receptor and comparison with the radio-ligand binding assay. Cytometry. 1994 Jul 1;16(3):262–269. doi: 10.1002/cyto.990160311. [DOI] [PubMed] [Google Scholar]
  5. Ferrero M., Spyratos F., Le Doussal V., Desplaces A., Rouëssé J. Flow cytometric analysis of DNA content and keratins by using CK7, CK8, CK18, CK19, and KL1 monoclonal antibodies in benign and malignant human breast tumors. Cytometry. 1990;11(6):716–724. doi: 10.1002/cyto.990110609. [DOI] [PubMed] [Google Scholar]
  6. Gullick W. J., Love S. B., Wright C., Barnes D. M., Gusterson B., Harris A. L., Altman D. G. c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer. 1991 Mar;63(3):434–438. doi: 10.1038/bjc.1991.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Howell A., Barnes D. M., Harland R. N., Redford J., Bramwell V. H., Wilkinson M. J., Swindell R., Crowther D., Sellwood R. A. Steroid-hormone receptors and survival after first relapse in breast cancer. Lancet. 1984 Mar 17;1(8377):588–591. doi: 10.1016/s0140-6736(84)90995-4. [DOI] [PubMed] [Google Scholar]
  8. Nicholson S., Sainsbury J. R., Needham G. K., Chambers P., Farndon J. R., Harris A. L. Quantitative assays of epidermal growth factor receptor in human breast cancer: cut-off points of clinical relevance. Int J Cancer. 1988 Jul 15;42(1):36–41. doi: 10.1002/ijc.2910420108. [DOI] [PubMed] [Google Scholar]
  9. Paik S., Hazan R., Fisher E. R., Sass R. E., Fisher B., Redmond C., Schlessinger J., Lippman M. E., King C. R. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990 Jan;8(1):103–112. doi: 10.1200/JCO.1990.8.1.103. [DOI] [PubMed] [Google Scholar]
  10. Perren T. J. c-erbB-2 oncogene as a prognostic marker in breast cancer. Br J Cancer. 1991 Mar;63(3):328–332. doi: 10.1038/bjc.1991.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Powles T. J., Trott P. A., Cherryman G., Clarke S., Ashley S., Coombes R. C., Jones A. L., Sinnett H. D., Nash A. G. Fine needle aspiration cytodiagnosis as a pre-requisite for primary medical treatment of breast cancer. Cytopathology. 1991;2(1):7–12. doi: 10.1111/j.1365-2303.1991.tb00378.x. [DOI] [PubMed] [Google Scholar]
  12. Sainsbury J. R., Malcolm A. J., Appleton D. R., Farndon J. R., Harris A. L. Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol. 1985 Nov;38(11):1225–1228. doi: 10.1136/jcp.38.11.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  14. Stål O., Sullivan S., Sun X. F., Wingren S., Nordenskjöld B. Simultaneous analysis of c-erbB-2 expression and DNA content in breast cancer using flow cytometry. Cytometry. 1994 Jun 1;16(2):160–168. doi: 10.1002/cyto.990160210. [DOI] [PubMed] [Google Scholar]
  15. Whiteside T. L., Miescher S., Hurlimann J., Moretta L., von Fliedner V. Clonal analysis and in situ characterization of lymphocytes infiltrating human breast carcinomas. Cancer Immunol Immunother. 1986;23(3):169–178. doi: 10.1007/BF00205646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wright C., Angus B., Nicholson S., Sainsbury J. R., Cairns J., Gullick W. J., Kelly P., Harris A. L., Horne C. H. Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res. 1989 Apr 15;49(8):2087–2090. [PubMed] [Google Scholar]
  17. Yuan J., Hennessy C., Corbett I. P., Dykin R., Givan A. L., Shenton B. K., Henry J. A., Wright C., Lennard T. W. Node negative breast cancer: the prognostic value of DNA ploidy for long-term survival. Br J Surg. 1991 Jul;78(7):844–848. doi: 10.1002/bjs.1800780724. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES