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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Atkin NB (1972) Modal deoxyribonucleic acid value and survival in carcinoma of the breast. Br Med J 1: 271–272
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
Auer GU, Caspersson TO, Wallgren AS (1980) DNA content and survival in mammary carcinoma. Anal Quant Cytol 2: 161–165
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
Auer GU, Fallenius AG, Erhardt KY, Sundel in BSB (1984b) Progression of mammary adenocarcinomas as reflected by nuclear DNA content. Cytometry 5: 420–425
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
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
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
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
Bishop JM (1987) The molecular genetics of cancer. Science 235: 305–311
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
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
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
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
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
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
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
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
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
Ewers SB, Langstrom E, Baldetorp B, Killander D (1984) Flow cytometric DNA analysis in primary breast carcinoma and clinicopathological correlations. Cytometry 5:408–419
Fallenius AG, Skoog LK, Svane GE, Auer (1984) Cytophotometrical and biochemical characterization of nonpalpable, mammographically detected mammary adenocarcinomas. Cytometry 5: 426–429
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
Friedlander ML, Hedley DW, Taylor IW (1984) Clinical and biological significance of aneuploidy in human tumours, a review. J Clin Pathol 37: 961–974
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
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
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)
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
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
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
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
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)
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
Joensua H, Klemi P, Eerola E, Tuominen J (1986) Influence of cellular DNA content on survival in differentiated thyroid cancer. Cancer 58: 2462–2467
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
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
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
Laerum OD, Farsund T (1981) Clinical application of flow cytometry: a review. Cytometry 2: 1–13
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
Look AT, Robertson RK, Williams DL (1985) Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukaemia. Blood 65: 1079–1086
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
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
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
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
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
Meyer JS, Friedman E, McCrate M, Bauer WG (1983) Prediction of early course of breast carcinoma by thymidine labeling. Cancer 51: 1879–1886
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
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
Sandberg AA (1980) The chromosomes in human cancer and leukaemia. Elsevier/North Holland, New York
Sandberg AA, Turc-Carel C (1987) The cytogenetics of solid tumors. Relation to diagnosis, classification and pathology. Cancer 59: 387–395
Shapiro H (1985) Practical flow cytometry. Liss New York
Silvestrini R, Daidone MG, Gasparini G (1985) Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56: 1982–1987
Taylor IW (1980) A rapid single step staining technique for DNA analysis by flow microfluorimetry. J Histochem Cytochem 28: 1021–1024
Taylor IW, Milthorpe BK (1980) An evaluation of DNA fluorochromes, staining techniques and analysis for flow cytometry. J Histochem Cytochem 28: 1224–1232
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
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
Tribukait B (1984a) Clinical DNA flow cytometry. Med Oncol Tumor Pharmacother 1: 211–218
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
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
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
Watson JV (1986) Oncogenes, cancer and analytical cytology. Cytometry 7: 400–410
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin · Heidelberg
About this chapter
Cite this chapter
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
Download citation
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
eBook Packages: Springer Book Archive