Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Nov;81(6):1017–1021. doi: 10.1038/sj.bjc.6690801

A high proliferation rate measured by cyclin A predicts a favourable chemotherapy response in soft tissue sarcoma patients

R L Huuhtanen 1, T A Wiklund 1, C P Blomqvist 1, T O Böhling 2, M J Virolainen 2, B Tribukait 3, L C Andersson 2,3
PMCID: PMC2362954  PMID: 10576659

Abstract

A small but not insignificant number of patients experience a prolonged survival after treatment of metastatic soft tissue sarcoma. This must be weighed against the majority of the patients who benefit little from the therapy, but nevertheless experience its side-effects. It would therefore be of utmost importance to be able to screen for those patients who respond to the treatment. Since proliferating cells are more sensitive to chemotherapy than non-proliferative cells, we measured the proliferation rate of the primary tumour of 55 soft tissue sarcoma patients with locally advanced or metastatic disease by determining the flow cytometric S phase fraction and immunohistochemical Ki-67 and cyclin A scores. S phase fraction or Ki-67 score did not predict chemotherapy response or progression-free survival. A high cyclin A score, however, correlated with a better chemotherapy response (P = 0.02) and longer progression-free survival time (P = 0.04). Our results suggest that a high cyclin A score predicts chemotherapy sensitivity. © 1999 Cancer Research Campaign

Keywords: soft tissue sarcoma, proliferation, chemotherapy response, cyclin A, Ki-67, S phase fraction

Full Text

The Full Text of this article is available as a PDF (70.8 KB).

Selected References

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

  1. Benjamin R. S., Rouëssé J., Bourgeois H., van Hoesel Q. G. Should patients with advanced sarcomas be treated with chemotherapy? . Eur J Cancer. 1998 Jun;34(7):958–965. doi: 10.1016/s0959-8049(98)00014-8. [DOI] [PubMed] [Google Scholar]
  2. Borden E. C., Amato D. A., Edmonson J. H., Ritch P. S., Shiraki M. Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas. Cancer. 1990 Sep 1;66(5):862–867. doi: 10.1002/1097-0142(19900901)66:5<862::aid-cncr2820660509>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  3. Gerdes J., Lemke H., Baisch H., Wacker H. H., Schwab U., Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984 Oct;133(4):1710–1715. [PubMed] [Google Scholar]
  4. Hahka-Kemppinen M., Muhonen T., Nordling S., Pyrhönen S. DNA flow cytometry and the outcome of chemoimmunotherapy in metastatic melanoma. Melanoma Res. 1997 Aug;7(4):329–334. doi: 10.1097/00008390-199708000-00008. [DOI] [PubMed] [Google Scholar]
  5. Hedley D. W. Flow cytometry using paraffin-embedded tissue: five years on. Cytometry. 1989 May;10(3):229–241. doi: 10.1002/cyto.990100302. [DOI] [PubMed] [Google Scholar]
  6. Heiden T., Wang N., Tribukait B. An improved Hedley method for preparation of paraffin-embedded tissues for flow cytometric analysis of ploidy and S-phase. Cytometry. 1991;12(7):614–621. doi: 10.1002/cyto.990120705. [DOI] [PubMed] [Google Scholar]
  7. Hietanen P., Blomqvist C., Wasenius V. M., Niskanen E., Franssila K., Nordling S. Do DNA ploidy and S-phase fraction in primary tumour predict the response to chemotherapy in metastatic breast cancer? Br J Cancer. 1995 May;71(5):1029–1032. doi: 10.1038/bjc.1995.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Huuhtanen R. L., Blomqvist C. P., Böhling T. O., Wiklund T. A., Tukiainen E. J., Virolainen M., Tribukait B., Andersson L. C. Expression of cyclin A in soft tissue sarcomas correlates with tumor aggressiveness. Cancer Res. 1999 Jun 15;59(12):2885–2890. [PubMed] [Google Scholar]
  9. Joensuu H., Ristamäki R., Söderström K. O., Jalkanen S. Effect of treatment on the prognostic value of S-phase fraction in non-Hodgkin's lymphoma. J Clin Oncol. 1994 Oct;12(10):2167–2175. doi: 10.1200/JCO.1994.12.10.2167. [DOI] [PubMed] [Google Scholar]
  10. Karlsson M., Jungnelius U., Aamdal S., Boeryd B., Carstensen J., Kågedal B., Westberg R., Wingren S. Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma. Int J Cancer. 1996 Jan 3;65(1):1–5. doi: 10.1002/(SICI)1097-0215(19960103)65:1<1::AID-IJC1>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  11. Mattern J., Wayss K., Volm M. Predicting chemosensitivity of tumors. Breast Cancer Res Treat. 1986;8(2):157–159. doi: 10.1007/BF01807704. [DOI] [PubMed] [Google Scholar]
  12. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  13. O'Reilly S. M., Camplejohn R. S., Rubens R. D., Richards M. A. DNA flow cytometry and response to preoperative chemotherapy for primary breast cancer. Eur J Cancer. 1992;28(2-3):681–683. doi: 10.1016/s0959-8049(05)80124-8. [DOI] [PubMed] [Google Scholar]
  14. Remvikos Y., Beuzeboc P., Zajdela A., Voillemot N., Magdelénat H., Pouillart P. Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy. J Natl Cancer Inst. 1989 Sep 20;81(18):1383–1387. doi: 10.1093/jnci/81.18.1383. [DOI] [PubMed] [Google Scholar]
  15. Saeter G., Alvegård T. A., Monge O. R., Strander H., Turesson I., Klepp R., Söderberg M., Wist E., Raabe N., Erlanson M. Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study. Eur J Cancer. 1997 Sep;33(10):1551–1558. doi: 10.1016/s0959-8049(97)00102-0. [DOI] [PubMed] [Google Scholar]
  16. Santoro A., Tursz T., Mouridsen H., Verweij J., Steward W., Somers R., Buesa J., Casali P., Spooner D., Rankin E. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537–1545. doi: 10.1200/JCO.1995.13.7.1537. [DOI] [PubMed] [Google Scholar]
  17. Schmidt R. A., Conrad E. U., 3rd, Collins C., Rabinovitch P., Finney A. Measurement and prediction of the short-term response of soft tissue sarcomas to chemotherapy. Cancer. 1993 Nov 1;72(9):2593–2601. doi: 10.1002/1097-0142(19931101)72:9<2593::aid-cncr2820720914>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  18. Schütte J., Mouridsen H. T., Stewart W., Santoro A., van Oosterom A. T., Somers R., Blackledge G., Verweij J., Dombernowsky P., Thomas D. Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma. The EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 1990;26(5):558–561. doi: 10.1016/0277-5379(90)90075-5. [DOI] [PubMed] [Google Scholar]
  19. Steward W. P., Verweij J., Somers R., Spooner D., Kerbrat P., Clavel M., Crowther D., Rouesse J., Tursz T., Tueni E. Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1993 Jan;11(1):15–21. doi: 10.1200/JCO.1993.11.1.15. [DOI] [PubMed] [Google Scholar]
  20. Stål O., Skoog L., Rutqvist L. E., Carstensen J. M., Wingren S., Sullivan S., Andersson A. C., Dufmats M., Nordenskjöld B. S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer. Br J Cancer. 1994 Dec;70(6):1258–1262. doi: 10.1038/bjc.1994.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Volm M., Koomägi R., Mattern J., Stammler G. Cyclin A is associated with an unfavourable outcome in patients with non-small-cell lung carcinomas. Br J Cancer. 1997;75(12):1774–1778. doi: 10.1038/bjc.1997.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Volm M., Rittgen W., Drings P. Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. Br J Cancer. 1998 Feb;77(4):663–669. doi: 10.1038/bjc.1998.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wiklund T. A., Blomqvist C. P., Virolainen M., Elomaa I. Ifosfamide, vincristine, doxorubicin and dacarbazine in adult patients with advanced soft-tissue sarcoma. Cancer Chemother Pharmacol. 1992;30(2):100–104. doi: 10.1007/BF00686400. [DOI] [PubMed] [Google Scholar]
  24. Wiklund T., Saeter G., Strander H., Alvegård T., Blomqvist C. The outcome of advanced soft tissue sarcoma patients with complete tumour regression after either chemotherapy alone or chemotherapy plus surgery. The Scandinavian Sarcoma Group experience. Eur J Cancer. 1997 Mar;33(3):357–361. doi: 10.1016/s0959-8049(97)89006-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES