Clinical Aspects of Assessing Cell Proliferation

  • S. M. O’Reilly
  • M. A. Richards


Despite the numerous studies which have assessed cell proliferation in tumours, measurement of proliferation indices has had, to date, little impact on patient management. This chapter will outline the techniques currently clinically available and discuss their practical advantages and disadvantages. In addition, the clinical situations in which assessment of cell proliferation may prove to be of use will be reviewed.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aherne WA, Al-Wiswazy M, Ford D and Jellerer AM (1977) Assessment of inherent fluctuations of mitotic and labelling indices of human tumours. Br J Cancer 36:577–591PubMedCentralPubMedGoogle Scholar
  2. Alexanian R, Gehan E, Haut A et al. (1978) Unmaintained remission in multiple myeloma. Blood 51:1005–1011PubMedGoogle Scholar
  3. Badalament RA, Hermansen DK, Kimmel M et al. (1987) The sensitivity of bladder wash flow cytometry, bladder wash cytology and voided cytology in the detection of bladder carcinoma. Cancer 60:1423–1427PubMedGoogle Scholar
  4. Baildam AD, Zaloudik J, Howell A et al. (1987) DNA analysis by flow cytometry, response to endocrine treatment and prognosis in advanced carcinoma of the breast. Br J Cancer 55:553–559PubMedCentralPubMedGoogle Scholar
  5. Baisch H, Beck H-P, Christensen IJ et al. (1982) A comparison of mathematical methods for the analysis of DNA histograms obtained by flow cytometry. Cell Tissue Kinet 15:235–249PubMedGoogle Scholar
  6. Barlogie B, Raber MN, Schumann J et al. (1983) Flow cytometry in clinical cancer research. Cancer Res 43:3982–3997PubMedGoogle Scholar
  7. Barnard NJ, Hall PA, Lemoine NR and Kadar N (1987) Proliferative index in breast carcinoma determined in situ by Ki-67 immunostaining and its relationship to clinical and pathological variables. J Pathol 152:287–295PubMedGoogle Scholar
  8. Bauer KD, Merkel DE, Winter JN et al. (1986) Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas. Cancer Res 46:3173–3178PubMedGoogle Scholar
  9. Bauer KD, Lincoln ST, Vera-Roman JM et al. (1987) Prognostic implications of proliferative activity and DNA aneuploidy in colonic adenocarcinomas. Lab Invest 57:329–335PubMedGoogle Scholar
  10. Benbow EW and Cromie CJ (1989) Inability of AgNOR counts to differentiate between bronchial carcinoid tumours and small cell carcinoma of the bronchus. J Clin Pathol 42:1003–1004PubMedGoogle Scholar
  11. Bertuzzi A, Daidone MG, Di Fronzo G and Silvestrini R (1981) Relationship among estrogen receptors, proliferative activity and menopausal status in breast cancer. Breast Cancer Res Treat 1:253–262PubMedGoogle Scholar
  12. Biasco G, Paganelli GM, Miglioli M et al. (1990) Rectal cell proliferation and colon cancer risk in ulcerative colitis. Cancer Res 50:1156–1159PubMedGoogle Scholar
  13. Bloom HJG and Richardson WW (1957) Histological grading and prognosis in breast cancer. A study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 9:359–377Google Scholar
  14. Boccadoro M, Gavarotti P, Fossati G et al. (1984) Low plasma cell 3(H)thymidine incorporation in monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma and remission phase myeloma: a reliable indicator of patients not requiring therapy. Br J Haematol 58:689–696PubMedGoogle Scholar
  15. Bonadonna G, Valagussa P and Tancini G et al. (1986) Current status of Milan adjuvant chemotherapy trials for node-positive and node-negative breast cancer. Natl Cancer Inst Monogr 1:45–49Google Scholar
  16. Brandt L, Olsson H and Monti M (1981) Uptake of thymidine in lymphoma cells obtained through fine needle aspiration biopsy: relation to prognosis in non-Hodgkin’s lymphoma. Eur J Cancer 17:1229–1233Google Scholar
  17. Bunn PA, Carney DN and Gazdar AF et al. (1983) Diagnostic and biological implications of flow cytometric DNA content analysis in lung cancer. Cancer Res 43:5026–5032PubMedGoogle Scholar
  18. Christopherson WM, Williamson FO and Gray IA (1972) Leiomyosarcoma of the uterus. Cancer 29:1512–1517PubMedGoogle Scholar
  19. Christov K, Milev A and Todorov V (1989) DNA aneuploidy and cell proliferation in breast tumours. Cancer 64:673–679PubMedGoogle Scholar
  20. Cibull ML, Heryet A, Gatter KC and Mason DY (1989) The utility of Ki-67 immunostaining, nucleolar organizer region counting and morphology in the assessment of follicular lymphomas. J Pathol 158:189–193PubMedGoogle Scholar
  21. Clark GM, Dressier LG and Owens MA et al. (1989) Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med 320:627–633PubMedGoogle Scholar
  22. Collste LG, Devonec M and Darzynkiewicz Z et al. (1980) Bladder cancer diagnosis by flow cytometry: correlation between cell samples from biopsy and bladder irrigation fluid. Cancer 45:2389–2394PubMedGoogle Scholar
  23. Cooke LD, Cooke TG, Bootz F et al. (1990) Ploidy as a prognostic indicator in end stage squamous cell carcinoma of the head and neck region treated with cisplatinum. Br J Cancer 61:759–762PubMedCentralPubMedGoogle Scholar
  24. Costa A, Bonadonna G, Villa E et al. (1981) Labelling index as a prognostic marker in non Hodgkin’s lymphoma. J Natl Cancer Inst 66:1–5PubMedGoogle Scholar
  25. Courdi A, Hery M, Dahan E et al. (1989) Factors affecting relapse in node-negative breast cancer: a multivariate analysis including labelling index. Eur J Cancer Clin Oncol 25:351–356PubMedGoogle Scholar
  26. Cowan RA, Harris M, Jones M and Crowther D (1989) DNA content in high and intermediate grade non-Hodgkin’s lymphoma - prognostic significance and clinicopathological correlations. Br J Cancer 60:904–910PubMedCentralPubMedGoogle Scholar
  27. Crocker J and Nar P (1987) Nucleolar organiser regions in lymphomas. J Pathol 151:111–118PubMedGoogle Scholar
  28. Crocker J and Skilbeck N (1987) Nucleolar organiser region associated proteins in cutaneous melanotic lesions: a quantitative study. J Clin Pathol 40:885–889PubMedGoogle Scholar
  29. Crocker J, Ay res J and McGovern J (1987) Nucleolar organiser regions in small cell carcinoma of the bronchus. Thorax 42:972–975PubMedGoogle Scholar
  30. Dean PN and Jett JH (1974) Mathematical analysis of DNA distributions derived from flow microfluorometry. J Cell Biol 60:523–527PubMedGoogle Scholar
  31. De Vere White R, Tesluk H and Deitcg A (1987) The paradox of aneuploidy in the benign and malignant prostate. Cytometry 1:3Google Scholar
  32. Diamond LW, Nathwani BN and Rappaport H (1982) Flow cytometry in the diagnosis and classification of malignant lymphoma and leukaemia. Cancer 50:1122–1135PubMedGoogle Scholar
  33. Dressier LG and Bartow SA (1989) DNA flow cytometry in solid tumours: practical aspects and clinical applications. Semin Diagn Pathol 6:55–82Google Scholar
  34. Dressier LG, Seamer L, Owens MA et al. (1987) Evaluation of a modelling system for S phase estimation in breast cancer by flow cytometry. Cancer Res 47:5294–5302Google Scholar
  35. Dressier LG, Seamer LC, Owens MA et al. (1988) DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens. Cancer 61:420–427Google Scholar
  36. Dressier LG, Eudey L, Gray R et al. (1990) DNA flow cytometry measurements are prognostic for time to recurrence in node negative breast cancer patients: an eastern Co-operative Group (ECOG) intergroup study. Proc Am Soc Clin Oncol 9:22Google Scholar
  37. Durie BGM (1986) Staging and kinetics of multiple myeloma. Semin Oncol 13:300–309PubMedGoogle Scholar
  38. Durie BGM, Salmon SE and Moon TE (1980) Pretreatment tumour mass, cell kinetics and prognosis in multiple myeloma. Blood 55:364–372PubMedGoogle Scholar
  39. Egan MJ, Raafat F, Crocker J and Smith K (1987) Nucleolar organiser regions in small cell tumours of childhood. J Pathol 153:275–280PubMedGoogle Scholar
  40. Egerton DA, Said JM, Epling S and Lee S (1988) DNA content of T-cell lymphomas. A flow cytometric analysis. Am J Pathol 130:326–334Google Scholar
  41. Ellis SJ and Whitehead R (1981) Mitoses counting: a need for reappraisal. Hum Pathol 12:3–4PubMedGoogle Scholar
  42. Ensley J, Maciorowski Z and Pietrazskiewicz H et al. (1990) Prospective correlation of cytotoxic response and DNA content parameters in advanced squamous cell cancer of the head and neck. Proc Am Soc Clin Oncol 9:173Google Scholar
  43. Fallowfield ME and Cook MG (1989) The value of nucleolar organiser region staining in the differential diagnosis of borderline melanocytic lesions. Histopathology 14:229–304Google Scholar
  44. Fallowfield ME, Dodson AR and Cook MG (1988) Nucleolar organiser regions in melanocytic dysplasia and melanoma. Histopathology 13:95–99PubMedGoogle Scholar
  45. Feichter GE, Mueller A and Kaufmann M et al. (1988) Correlations of DNA flow cytometric results and other prognostic factors in primary breast cancer. Int J Cancer 41:823–828PubMedGoogle Scholar
  46. Fisher B, Bauer M, Wickerham L et al. (1983) Relationship of the number of positive axillary nodes to the prognosis of patients with primary breast cancer. Cancer 52:1551–1557PubMedGoogle Scholar
  47. Fossa SD, Thorud E, Shoaib MC et al. (1984) DNA flow cytometry in primary breast carcinoma. Acta Pathol Microbiol Scand 92:475–480Google Scholar
  48. Franzen G, Klintenberg C, Olofsson J and Risberg B (1986) DNA measurement - an objective predictor of response to irradiation. Br J Cancer 53:643PubMedCentralPubMedGoogle Scholar
  49. Gentili C, Sanfilippo O and Silvestrini R (1981) Cell proliferation and its relationship to clinical features and relapse in breast cancers. Cancer 48:974–979PubMedGoogle Scholar
  50. Gerdes J, Pickartz H, Brotherton J et al. (1987) Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies. Am J Pathol 129:486–492PubMedGoogle Scholar
  51. Giri DD, Nottingham JF, Lawry J et al. (1989) Silver binding nucleolar organizer regions (AgNORs) in benign and malignant breast lesions: correlations with ploidy and growth phase by DNA flow cytometry. J Pathol 157:307–313PubMedGoogle Scholar
  52. Grant CS, Hay ID, Dyan JJ et al. (1990) Diagnostic and prognostic utility of flow cytometric DNA measurements in follicular thyroid tumours. World J Surg 14:283–290PubMedGoogle Scholar
  53. Greipp PR and Kyle RA (1983) Clinical, morphological and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance and smouldering multiple myeloma. Blood 62:166–171PubMedGoogle Scholar
  54. Haag D, Goerttler M and Tschahargane C (1984) The proliferative index of human breast cancer as obtained by flow cytometry. Pathol Res Pract 178:315–322PubMedGoogle Scholar
  55. Hall PA and Levison DA (1990) Assessment of cell proliferation in histological material. J Clin Pathol 43:184–192PubMedGoogle Scholar
  56. Hall PA, Crocker J, Watts A and Stansfeld AG (1988a) A comparison of nucleolar organizer region staining and Ki-67 immunostaining in non-Hodgkin’s lymphoma. Histopathol 12:373–381Google Scholar
  57. Hall PA, Richards MA, Gregory WM et al. (1988b) The prognostic value of Ki-67 immunostaining in non-Hodgkin’s lymphoma. J Pathol 154:223–225PubMedGoogle Scholar
  58. Hanby AM, Hall PA, Gregory WM, Dennis P, Rooney N, James P, Richman PI and Levison DA (1990) An inter and intra-observer study on the diagnosis of lymph node biopsies. J Pathol 161:345aGoogle Scholar
  59. Hart WR and Billman JK (1978) A reassessment of uterine neoplasms originally diagnosed as leiomyosarcomas. Cancer 41:1902–1910PubMedGoogle Scholar
  60. Hedley DW, Rugg CA and Gelber RD (1987) Association of DNA index and S phase fraction with prognosis in nodes positive breast early breast cancer. Cancer Res 47:4729–4735PubMedGoogle Scholar
  61. Holt S, Croton R, Leinster SJ et al. (1986) In vitro thymidine labelling index in primary operable breast cancer. Eur J Surg Oncol 12:53–57PubMedGoogle Scholar
  62. Kallioniemi O-P, Hietanen T, Mattila J et al. (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 23:277–282PubMedGoogle Scholar
  63. Kallioniemi O-P, Punnonen R, Mattila J et al. (1988) Prognostic significance of DNA index, multiploidy and S phase fraction in ovarian cancer. Cancer 61:334–339PubMedGoogle Scholar
  64. Klintenberg C, Stal O, Nordenskjold B et al. (1986) Proliferative index, cytosolic estrogen receptor and axillary node status as prognostic predictors in human mammary cancer. Breast Cancer Res Treat 7(suppl):99–106Google Scholar
  65. Kute TE, Muss HB, Anderson D et al. (1981) Relationship of steroid receptor, cell kinetics and clinical status in patients with breast cancer. Cancer Res 41:3524–3529PubMedGoogle Scholar
  66. Kute TE, Muss HB, Hopkins M et al. (1985) Relationship of flow cytometry results to clinical and steroid receptor status in human breast cancer. Breast Cancer Res Treat 6:113–121PubMedGoogle Scholar
  67. Kvalov S, Morton PF, Kaalhus O et al. (1985) [3H]thymidine uptake in B cell lymphomas. Relationship to treatment response and survival. Scand J Haematol 34:429–435Google Scholar
  68. Lipkin M, Blattner WE, Fraumeni JF et al. (1983) Tritiated thymidine (Ψp, Ψh) labelling distribution as a marker for hereditary predisposition to colon cancer. Cancer Res 43:1899–1904PubMedGoogle Scholar
  69. Lykkesfeldt AE, Balsev I, Christensen IJ et al. (1988) DNA ploidy and S phase fraction in primary breast carcinomas in relation to prognostic factors and survival for premenopausal patients at high risk for recurrent disease. Acta Oncol 27:749–756PubMedGoogle Scholar
  70. Macartney JC and Camplejohn RS (1990) DNA flow cytometry in non-Hodgkins lymphomas. Eur J Cancer 26:635–637PubMedGoogle Scholar
  71. Macartney JC, Camplejohn RS, Alder J et al. (1986) Prognostic importance of DNA flow cytometry in non-Hodgkin’s lymphomas. J Clin Pathol 39:542–546PubMedGoogle Scholar
  72. Mason BH (1983) Progesterone and estrogen receptors as prognostic variables in breast cancer. Cancer Res 43:2985–2990PubMedGoogle Scholar
  73. Meyer JS and Hixon B (1979) Advanced stage and early relapse of breast carcinomas associated with high thymidine labelling indices. Cancer Res 39:4041–4047Google Scholar
  74. Masters JRW, Camplejohn RS, Millis RR and Rubens RD (1987) Histological grade, elastosis, DNA ploidy and the response to chemotherapy of breast cancer. Br J Cancer 55:455–457PubMedCentralPubMedGoogle Scholar
  75. McDivitt RW, Stone KR, Craig RB and Meyer JS (1985) A comparison of human breast cancer cell kinetics measured by flow cytometry and thymidine labelling. Lab Invest 52:287–291PubMedGoogle Scholar
  76. McDivitt RW, Stone KR, Craig RB et al. (1986) A proposed classification of breast cancer based on kinetic information. Cancer 57:269–276PubMedGoogle Scholar
  77. McFarlane JH, Quirke P and Bird CC (1986) Flow cytometric analysis of DNA heterogeneity in non-Hodgkin’s lymphoma. J Pathol 149:236Google Scholar
  78. McGurrin JF, Doria MI, Dawson PJ et al. (1987) Assessment of tumour cell kinetics by immunohistochemistry in carcinoma of breast. Cancer 59:1744–1750PubMedGoogle Scholar
  79. Merkel DE and McGuire WL (1990) Ploidy, proliferative activity and prognosis: DNA flow cytometry of solid tumours. Cancer 65:1194–1295PubMedGoogle Scholar
  80. Meyer JS and Prioleau PG (1981) S phase fractions of colorectal carcinomas related to pathologic and clinical features. Cancer 48:1221–1228PubMedGoogle Scholar
  81. Meyer JS, Friedman E, McCrate MM and Bauer WC (1983) Prediction of early course of breast carcinoma by thymidine labelling. Cancer 51:1879–1886PubMedGoogle Scholar
  82. Meyer JS, Prey MU, Babcock DS and McDivitt RW (1986) Breast carcinome cell kinetics, morphology, stage and host characteristics. Lab Invest 54:41–51PubMedGoogle Scholar
  83. Moran RE, Black MM, Alpert L and Straus MJ (1984) Correlation of cell-cycle kinetics, hormone receptors, histopathology and nodal status in human breast cancer. Cancer 54:1586–1590PubMedGoogle Scholar
  84. Muss HB, Kute TE, Case LD et al. (1989) The relation of flow cytometry to clinical and biologic characteristics in women with node negative primary breast cancer. Cancer 64:1894–1900PubMedGoogle Scholar
  85. NCI Non-Hodgkin’s Lymphoma Classification Project Writing Committee (1985) Classification of non-Hodgkin’s lymphomas. Cancer 55:9Google Scholar
  86. Nemoto T, Vana J, Bedwani R et al. (1980) Management and survival of female breast cancer: Results of a national survey by the American College of Surgeons. Cancer 45:2917–2924PubMedGoogle Scholar
  87. O’Reilly SM, Camplejohn RS, Barnes DM et al. (1990a) DNA index, S phase fraction, histological grade and prognosis in breast cancer. Br J Cancer 61:671–674PubMedCentralPubMedGoogle Scholar
  88. O’Reilly SM, Camplejohn RS, Millis RR et al. (1990b) Node negative breast cancer: prognostic subgroups defined by tumour size and flow cytometry. J Clin Oncol 8:2040–2046PubMedGoogle Scholar
  89. O’Reilly SM, Camplejohn RS, Millis RR et al. (1990c) Proliferative activity, histological grade and benefit from adjuvant chemotherapy in node positive breast cancer. Eur J Cancer 26:1035–1038PubMedGoogle Scholar
  90. Olszewski W, Darzynkiewicz Z, Rosen PP et al. (1981) Flow cytometry of breast carcinoma: relation of tumour cell cycle distribution to histology and estrogen receptor. Cancer 48:985–988PubMedGoogle Scholar
  91. Ploton D, Menager M, Jeannesson P et al. (1986) Improvement in the staining and visualisation of the argyrophilic proteins of the nucleolar organiser region at the optical level. Histochem J 18:5–14PubMedGoogle Scholar
  92. Quinn CM and Wright NA (1990) The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol 160:93–102PubMedGoogle Scholar
  93. Raber MN, Barlogie B, Latreille J et al. (1982) Ploidy, proliferative activity and estrogen receptor content in human breast cancer. Cytometry 3:36–41PubMedGoogle Scholar
  94. Rehn S, Glimelius B, Strang P et al. (1990) Prognostic significance of flow cytometry studies in B-cell non-Hodgkin’s lymphoma. Haematol Oncol 8:1–12Google Scholar
  95. Remvikos Y, Lavee C, Vilcoq JR et al. (1990) Proliferative activity, response to neo-adjuvant chemotherapy and prognosis in stage II breast cancer. Breast Cancer Res Treat 16:190 (abstr)Google Scholar
  96. Richards MA, Gregory WM and Lister TA (1987) Prognostic factors in lymphoma. In: Stoll BA (ed) Prognostic factors in cancer. Elsevier, Amsterdam, pp 333–357Google Scholar
  97. Schrape S, Jones DB and Wright DH (1987) A comparison of three methods for the determination of the growth fraction in non-Hodgkin’s lymphoma. Br J Cancer 55:283–286PubMedCentralPubMedGoogle Scholar
  98. Schutte B, Reynders MM J, Wiggers T et al. (1987) Retrospective analysis of the prognostic significance of DNA content and proliferative activity in large bowel carcinoma. Cancer Res 47:5494–5496PubMedGoogle Scholar
  99. Sciallero S, Bruno S, Di Vinci A et al. (1988) Flow cytometric DNA ploidy in colorectal adenomas and family history of colorectal cancer. Cancer 61:114–120PubMedGoogle Scholar
  100. Sigurdsson H, Baldetorp B, Borg A et al. (1990) Indicators of prognosis in node negative breast cancer. N Engl J Med 322:1045–1053PubMedGoogle Scholar
  101. Silvestrini R, Daidone MG and Gasparini G (1985) Cell kinetics as a prognostic marker in node-negative breast cancer. Cancer 56:1982–1987PubMedGoogle Scholar
  102. Silvestrini R, Costa A, Veneroni S et al. (1988a) Comparative analysis of different approaches to investigate cell kinetics. Cell Tissue Kinet 21:123–131PubMedGoogle Scholar
  103. Silvestrini R, Daidone MG, Selvi et al. (1988b) Cell kinetics as a prognostic indicator in operable breast cancer: updated report. Proc Am Soc Clin Oncol 7:24Google Scholar
  104. Smith R and Crocker J (1988) Evaluation of nucleolar organiser region associated proteins in breast malignancy. Histopathology 12:113–125PubMedGoogle Scholar
  105. Srigley J, Barlogie B, Butler JJ et al. (1985) Heterogeneity of non-Hodgkin’s lymphoma probed by nucleic acid cytometry. Blood 65:1090–1096PubMedGoogle Scholar
  106. Stal O, Wingren S, Cartensen J et al. (1989) Prognostic value of DNA ploidy and S phase fraction in relation to estrogen receptor content and clinicopathological variables in primary breast cancer. Eur J Cancer Clin Oncol 25:301–309PubMedGoogle Scholar
  107. Stuart-Harris R, Hedley DW, Taylor IW et al. (1985) Tumour ploidy, response and survival in patients receiving endocrine therapy for advanced breast cancer. Br J Cancer 51:573PubMedCentralPubMedGoogle Scholar
  108. Suarez V, Newman J, Hiley C et al. (1989) The value of NOR numbers in neoplastic and non-neoplastic epithelium of the stomach. Histopathology 14:61–66PubMedGoogle Scholar
  109. Sulkes A, Livingston RB and Murphy WK (1979) Tritiated thymidine labelling index and response in human breast cancer. J Natl Cancer Inst 62:513–515PubMedGoogle Scholar
  110. Taylor HB and Norris HJ (1966) Mesenchymal tumours of the uterus. IV. Diagnosis and prognosis of leiomyosarcomas. Arch Pathol 82:40–44PubMedGoogle Scholar
  111. Ten Velde GPM, Schutte B, Roos M et al. (1988) Flow cytometric analysis of DNA ploidy level in paraffin-embedded tissue of non-small cell lung cancer. Eur J Cancer Clin Oncol 24:445–460Google Scholar
  112. Terpstra OT, van Blankenstein M, Dees J and Eilers GU (1987) Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology 92:704–708PubMedGoogle Scholar
  113. Toikkanen S, Joensuu H and Klemi P (1989) The prognostic significance of nuclear DNA content in invasive breast cancer - a study with long-term follow-up. Br J Cancer 60:693–700PubMedCentralPubMedGoogle Scholar
  114. Tubiana M and Malaise E (1976) Comparison of cell proliferation kinetics in human and experimental tumours: response to irradiation. Cancer Treat Rep 60:1887–1895PubMedGoogle Scholar
  115. Tubiana M, Pejovic MJ, Renaud A et al. (1981) Kinetic parameters and the course of the disease in breast cancer. Cancer 47:937–943PubMedGoogle Scholar
  116. Straus MJ, Moran R, Muller RE and Wotiz HH (1982) Estrogen receptor heterogeneity and the relationship between estrogen receptor and the tritiated thymidine labelling index in human breast cancer. Oncology 39:197–200PubMedGoogle Scholar
  117. Volm M, Drings P, Mattern J et al. (1985) Prognostic significance of DNA patterns and resistance predictive tests in non-small cell lung carcinoma. Cancer 56:1396–1403PubMedGoogle Scholar
  118. Walker RA (1988) The histopathological evaluation of nucleolar organiser region proteins. Histopathology 12:221–223PubMedGoogle Scholar
  119. Winter JN, Bauer K, Andersen J et al. (1989) Aneuploidy but not proliferative activity is associated with failure to remit in the diffuse aggressive lymphomas. Proc Am Assoc Cancer Res 30:36Google Scholar
  120. Wooldrige TN, Grierson HL, Weisenburger DD et al. (1988) Association of DNA content and proliferative activity with clinical outcome in patient with diffuse mixed cell and large cell non-Hodgkin’s lymphoma. Cancer Res 48:6608–6613Google Scholar
  121. Yang P, Huang GS and Zhu XS (1990) Role of nucleolar organiser regions in differentiating malignant from benign tumours of the colon. J Clin Pathol 43:235–238PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 1992

Authors and Affiliations

  • S. M. O’Reilly
  • M. A. Richards

There are no affiliations available

Personalised recommendations