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Measurement of DNA Content of Archival Material as a Guide to Prognosis

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High-Risk Breast Cancer
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Abstract

Flow cytometry is capable of measuring total DNA content of tens of thousands of cancer cells in minutes, with high precision. From such analyses two distinct and potentially important pieces of information are obtained; tumour DNA index (ploidy) and the percentage of cells in S-phase (% S-phase). There is currently optimism that this information will help in the identification of high risk breast cancer patients, and DNA flow cytometry is indeed now being offered on a routine clinical basis in the United States. Unfortunately, most of the published studies used fresh frozen material submitted for steroid hormone receptor analysis, and clinical follow-up is at best incomplete. The use of paraffin-embedded archival material allows the retrospective analysis of DNA content from defined cohorts of patients with known clinical outcome. This chapter outlines the techniques of DNA flow cytometry, with emphasis on the use of paraffin-embedded material, and reviews the results from three large, recently published series. Although DNA index appears to be a relatively weak prognostic indicator, preliminary results show that % S-phase, which is strongly linked to both nuclear grade and labelling index, could prove a clinically valuable measure of inherent biological aggression.

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References

  1. Atkin NB (1972) Modal deoxyribonucleic acid value and survival in carcinoma of the breast. Br Med J 1: 271–272

    Article  PubMed  CAS  Google Scholar 

  2. Atkin NB, Kay R (1979) Prognostic significance of modal DNA value and other factors in malignant tumours, based on 1465 cases. Br J Cancer 40: 210–221

    Article  PubMed  CAS  Google Scholar 

  3. Auer GU, Caspersson TO, Wallgren AS (1980) DNA content and survival in mammary carcinoma. Anal Quant Cytol 2: 161–165

    PubMed  CAS  Google Scholar 

  4. Auer GU, Eriksson E, Azavedo E, Caspersson T, Wallgren A (1984a) Prognostic significance of nuclear DNA content in mammary adenocarcinomas in humans. Cancer Res 44: 394–396

    PubMed  CAS  Google Scholar 

  5. Auer GU, Fallenius AG, Erhardt KY, Sundel in BSB (1984b) Progression of mammary adenocarcinomas as reflected by nuclear DNA content. Cytometry 5: 420–425

    Article  PubMed  CAS  Google Scholar 

  6. Barlogie B, Gohde W, Johnston DA, Smallwood L, Schumann J, Drewinko B, Freireich EJ (1978) Determination of ploidy and proliferative characteristics of human solid tumours by pulse cytophotometry. Cancer Res 38: 3333–3339

    PubMed  CAS  Google Scholar 

  7. Barlogie B, Johnston DA, Smallwood L, Raber MN, Maddox AM, Latreille J, Swartzendruber DE, Drewinko B (1982) Prognostic implications of ploidy and proliferative activity in human solid tumours. Cancer Genet Cytogenet 6: 17–28

    Article  PubMed  CAS  Google Scholar 

  8. Barlogie B, Raber MN, Schumann J, Johnson TS, Drewinko B, Swartzendruber DE, Gohde W, Andreef M, Freireich EJ (1983) Flow cytometry in cancer clinical research. Cancer Res 43: 3982–3997

    PubMed  CAS  Google Scholar 

  9. Bauer KD, Merkel DE, Winter JN, Marder RJ, Hauck WW, Wallemark CB, Williams TS, Variakojis D (1986) Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas. Cancer Res 46: 3173–3178

    PubMed  CAS  Google Scholar 

  10. Bishop JM (1987) The molecular genetics of cancer. Science 235: 305–311

    Article  PubMed  CAS  Google Scholar 

  11. Bonadonna G, Valagussa P, Tancini G, Rossi A, Brambilla C, Zambetti M, Bignami P, diFronzo G, Silvestrini R (1986) Current status of Milan adjuvant chemotherapy trials for node-positive and node-negative breast cancer. Natl Cancer Inst Monogr 1: 45–49

    Google Scholar 

  12. Bunn PA, Carney DN, Gazdar AF, Whang-Peng J, Matthews MJ (1983) Diagnostic and biological implications of flow cytometric DNA content analysis in lung cancer. Cancer Res 43: 5026–5032

    PubMed  CAS  Google Scholar 

  13. Christensson B, Tribukait B, Linder I-L, Ullman B, Biberfeld P (1986) Cell proliferation and DNA content in non-Hodgkin’s lymphoma. Flow cytometry in relation to lymphoma classification. Cancer 58: 1295–1304

    Article  PubMed  CAS  Google Scholar 

  14. Cornelisse CJ, deKoning HR, Moolenaar AJ, van de Velde CJ, Ploem JS (1984) Image and flow cytometric analysis of DNA content in breast cancer. Relation to estrogen receptor content and lymph node involvement. Anal Quant Cytol Histol 6: 9–18

    CAS  Google Scholar 

  15. Cornelisse CJ, van Driel-Kulker AM (1985) DNA image cytometry on machine-selected breast cancer cells and a comparison between flow cytometry and scanning cytophotometry. Cytometry 6: 471–477

    Article  PubMed  CAS  Google Scholar 

  16. Cornelisse CJ, van de Velde CJH, Caspers RJC, Moolenaar AJ, Hermass J (1987) DNA ploidy and survival in breast cancer patients. Cytometry 8: 225–234

    Article  PubMed  CAS  Google Scholar 

  17. Coulson PB, Thornthwaite JT, Wolley TW, Sugarbaker EV, Seckinger D (1984) Prognostic indicators including DNA histogram type, receptor content, and staging related to human breast cancer patient survival. Cancer Res. 44: 4187–4196

    PubMed  CAS  Google Scholar 

  18. Dowle CS, Owainati A, Riobirns A, Burns K, Ellis IO, Elston CW, Blamey RW (1987) Prognostic significance of the DNA content of human breast cancer. Br J Surg 74: 133–136

    Article  PubMed  CAS  Google Scholar 

  19. Dressier LG, Owens M, Seamer L, McGuire WL (1986) Identifying breast cancer patients for adjuvant therapy by DNA flow cytometry and steroid receptors: a 1000 patient study. Proc Am Soc Clin Oncol 5: 61

    Google Scholar 

  20. Ewers SB, Langstrom E, Baldetorp B, Killander D (1984) Flow cytometric DNA analysis in primary breast carcinoma and clinicopathological correlations. Cytometry 5:408–419

    Article  PubMed  CAS  Google Scholar 

  21. Fallenius AG, Skoog LK, Svane GE, Auer (1984) Cytophotometrical and biochemical characterization of nonpalpable, mammographically detected mammary adenocarcinomas. Cytometry 5: 426–429

    Article  PubMed  CAS  Google Scholar 

  22. Finan PJ, Quirke P, Dixon MF, Dyson JED, Giles GR, Bird CC (1986) Is DNA aneuploidy a good prognostic indicator in patients with advanced colorectal cancer? Br J Cancer 54: 327–330

    Article  PubMed  CAS  Google Scholar 

  23. Friedlander ML, Hedley DW, Taylor IW (1984) Clinical and biological significance of aneuploidy in human tumours, a review. J Clin Pathol 37: 961–974

    Article  PubMed  CAS  Google Scholar 

  24. Friedlander ML, Hedley DW, Taylor IW, Russell P, Coates AS, Tattersall M (1984) Influence of cellular DNA content on survival in advanced ovarian cancer. Cancer Res 44: 397–400

    PubMed  CAS  Google Scholar 

  25. Gansler T, Chatten J, Varello M, Bunin GR, Atkinson B (1986) Flow cytometric DNA analysis of neuroblastoma. Correlation with histology and clinical outcome. Cancer 58: 2453–2458

    Article  PubMed  CAS  Google Scholar 

  26. Harvey J, deKlerk N, Berryman I, Sterrett G, Byrne M, Papadimitriou J (1987) Nuclear DNA content and prognosis in human breast cancer. Breast Cancer Res Treat (In press)

    Google Scholar 

  27. Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA (1983) Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem 31: 1333–1335

    Article  PubMed  CAS  Google Scholar 

  28. Hedley DW, Rugg CA, Ng ABP, Taylor IW (1984) Influence of cellular DNA content on disease-free survival of stage II breast cancer patients. Cancer Res 44: 5395–5398

    PubMed  CAS  Google Scholar 

  29. Hedley DW, Friedlander ML, Taylor IW (1985) Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance. Cytometry 6: 327–333

    Article  PubMed  CAS  Google Scholar 

  30. Hedley DW, Leary JA, Kirsten F (1985) Metastatic adenocarcinoma of unknown primary site: abnormalities of cellular DNA content and survival. Eur J Cancer Clin Oncol 21: 185–189

    Article  PubMed  CAS  Google Scholar 

  31. Hedley DW, Rugg Ca, Gelber RD (1987) Association of DNA index and S-phase fraction with prognosis of nodes positive early breast cancer. Cancer Res 47: (In press)

    Google Scholar 

  32. Jakobsen A, Poulsen S, Madsen EL, Petersen SE, Hansen HS (1984) Ploidy level of human breast carcinoma. Relation to histopathologic features and hormone receptor content. Acta Radiol [Oncol] 23 (2–3): 103–107

    Article  CAS  Google Scholar 

  33. Joensua H, Klemi P, Eerola E, Tuominen J (1986) Influence of cellular DNA content on survival in differentiated thyroid cancer. Cancer 58: 2462–2467

    Article  Google Scholar 

  34. Kallioniemi O-P, Hietanen T, Mattila J, Lehtinen M, Lauslahti K, Koivula T (1987) Aneuploid DNA content and high S-phase fraction of tumour cells are related to poor prognosis in patients with primary breast cancer. Eur J Cancer Clin Oncol 23: 277–282

    Article  PubMed  CAS  Google Scholar 

  35. Kute TE, Muss HB, Anderson D, Crumb K, Miller B, Burns D, Drube LA (1981) Relationship of steroid receptor, cell kinetics and clinical status in patients with breast cancer. Cancer Res 41: 3524–3529

    PubMed  CAS  Google Scholar 

  36. Kute TE, Muss HB, Hopkins M, Marshall R, Case D, Kammire L (1985) Relationship of flow cytometry results to clinical and steroid receptor status in human breast cancer. Breast Cancer Res Treat 6: 113–121

    Article  PubMed  CAS  Google Scholar 

  37. Laerum OD, Farsund T (1981) Clinical application of flow cytometry: a review. Cytometry 2: 1–13

    Article  PubMed  CAS  Google Scholar 

  38. Look AT, Hayes A, Nitschke R, McWilliams NB, Green AA (1984) Cellular DNA content as a prediction of response to chemotherapy in infants with unresectable neuroblastoma. N Engl J Med 311: 231–235

    Article  PubMed  CAS  Google Scholar 

  39. Look AT, Robertson RK, Williams DL (1985) Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukaemia. Blood 65: 1079–1086

    PubMed  CAS  Google Scholar 

  40. McDivitt RW, Stone KR, Meyer JS (1984) A method for dissociation of viable human breast cancer cells that produces flow cytometric kinetic information similar to that obtained by thymidine labelling. Cancer Res 44: 2628–2633

    PubMed  CAS  Google Scholar 

  41. McDivitt RW, Stone UR, Craig RB, Palmer OS, Meyer JS, Bauer WC (1986) A proposed classification of breast cancer based on kinetic information. Derived from a comparison of risk factors in 168 primary operable breast cancers. Cancer 57: 269–276

    Article  PubMed  CAS  Google Scholar 

  42. Macartney JC, Camplejohn RS, Alder J, Stone MG, Powell G (1986) Prognostic importance of DNA flow cytometry in non-Hodgkin’s lymphomas. J Clin Pathol 39: 542–546

    Article  PubMed  CAS  Google Scholar 

  43. Mauro F, Teodori L, Schumann J, Gohde W (1986) Flow cytometry as a tool for the prognostic assessment of human neoplasia. Int J Radiat Oncol Biol Phys 12: 625–636

    Article  PubMed  CAS  Google Scholar 

  44. Meyer JS, Lee JY (1980) Relationship of S-phase fraction of breast carcinoma in relapse to duration of remission, estrogen receptor content, therapeutic responsiveness, and duration of survival. Cancer Res. 40: 1890–1896

    PubMed  CAS  Google Scholar 

  45. Meyer JS, Friedman E, McCrate M, Bauer WG (1983) Prediction of early course of breast carcinoma by thymidine labeling. Cancer 51: 1879–1886

    Article  PubMed  CAS  Google Scholar 

  46. Otto U, Baisch H, Huland H, Kloppel G (1984) Tumour cell deoxyribonucleic acid content and prognosis in human renal cell carcinoma. J Urol 132: 237–239

    PubMed  CAS  Google Scholar 

  47. Raber MN, Barlogie B, Latreille J, Bedrossian C, Fritsche H, Blumenschein G (1982) Ploidy, proliferative activity and estrogen receptor content in human breast cancer. Cytometry 3: 36–41

    Article  PubMed  CAS  Google Scholar 

  48. Sandberg AA (1980) The chromosomes in human cancer and leukaemia. Elsevier/North Holland, New York

    Google Scholar 

  49. Sandberg AA, Turc-Carel C (1987) The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer 59: 387–395

    Article  PubMed  CAS  Google Scholar 

  50. Shapiro H (1985) Practical flow cytometry. Liss New York

    Google Scholar 

  51. Silvestrini R, Daidone MG, Gasparini G (1985) Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56: 1982–1987

    Article  PubMed  CAS  Google Scholar 

  52. Taylor IW (1980) A rapid single step staining technique for DNA analysis by flow microfluorimetry. J Histochem Cytochem 28: 1021–1024

    Article  PubMed  CAS  Google Scholar 

  53. Taylor IW, Milthorpe BK (1980) An evaluation of DNA fluorochromes, staining techniques and analysis for flow cytometry. J Histochem Cytochem 28: 1224–1232

    Article  PubMed  CAS  Google Scholar 

  54. Taylor IW, Musgrove EA, Friedlander ML, Foo MS, Hedley DW (1983) The influence of age on the DNA ploidy levels of breast tumours. Eur J Cancer Clin Oncol 19: 623–628

    Article  PubMed  CAS  Google Scholar 

  55. Tribukait B, Hammarberg C, Rubio C (1983) Ploidy and proliferation patterns in colorectal adenocarcinomas related to Duke’s classification and to histopathological differentiation. A flow cytometric DNA study. Acta Pathol Microbiol Immunol Scand [A] 91: 89–95

    CAS  Google Scholar 

  56. Tribukait B (1984a) Clinical DNA flow cytometry. Med Oncol Tumor Pharmacother 1: 211–218

    PubMed  CAS  Google Scholar 

  57. Tribukait B (1984b) Flow cytometry in surgical pathology and cytology of tumors of the genito-urinary tract. In: Koss LG, Coleman DV (eds) Advances in clinical cytology, vol 2. Masson, New York, pp 163–189

    Google Scholar 

  58. Tubiana M, Pejovic MH, Chavaudra N, Contesso G, Malaise E (1984) The long-term prognostic significance of thymidine labelling index in breast cancer. Int J Cancer 33. 441–445

    Article  PubMed  CAS  Google Scholar 

  59. Volm M, Drings P, Mattern J, Sonka J, Vogt-Moykopf I, Wayss K (1985) Prognostic significance of DNA patterns and resistance-predictive tests in non-small cell lung carcinoma. Cancer 56: 1396–1403

    Article  PubMed  CAS  Google Scholar 

  60. Watson JV (1986) Oncogenes, cancer and analytical cytology. Cytometry 7: 400–410

    Article  PubMed  CAS  Google Scholar 

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© 1989 Springer-Verlag Berlin · Heidelberg

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Hedley, D.W. (1989). Measurement of DNA Content of Archival Material as a Guide to Prognosis. In: Ragaz, J., Ariel, I.M. (eds) High-Risk Breast Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73718-3_5

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  • DOI: https://doi.org/10.1007/978-3-642-73718-3_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73720-6

  • Online ISBN: 978-3-642-73718-3

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