Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1993 Oct;46(10):948–952. doi: 10.1136/jcp.46.10.948

Prognostic importance of DNA flow cytometric variables in rhabdomyosarcomas.

L C Wijnaendts 1, J C van der Linden 1, P van Diest 1, A J van Unnik 1, J F Delemarre 1, P A Voûte 1, C J Meijer 1
PMCID: PMC501625  PMID: 8227415

Abstract

AIM--To determine whether DNA ploidy patterns and S phase fraction offer prognostic information in patients with rhabdomyosarcoma (RMS). METHODS--DNA flow cytometry was performed on formalin fixed, paraffin wax embedded samples from primary tumours, and metastatic deposits or recurrences in 70 patients. DNA histogram analysis was done using a semi-automated cell cycle analysis program. RESULTS--Of the 70 primary tumours, 23 were DNA diploid, 32 DNA aneuploid, eight DNA multiploid, and seven DNA tetraploid. The prognosis for DNA aneuploid patterns was favourable, intermediate within the group of DNA tetraploid tumours and poor among patients with DNA diploid and DNA multiploid tumours (p = 0.009). In multivariate analysis (Cox regression model) DNA ploidy was an important independent prognostic factor, along with TNM stage, localisation, and histopathological classification. Ten out of 32 patients with a high S phase fraction (> 15%) with primary RMS achieved long term survival in contrast to 20 out of 29 patients with a low S phase fraction (< or = 15%) (p = 0.008). In 24 cases the DNA ploidy of cases of relapse was analysed. Of the 15 cases, in which stem line changes had occurred, 13 died of disease. No stem line changes were noted in nine cases and in this group four patients died of disease (p = 0.02). CONCLUSIONS--Assessment of DNA ploidy and S phase fraction in primary RMS and evaluation of stem line changes in cases of relapse are important variables in predicting prognosis.

Full text

PDF
948

Selected References

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

  1. Allsbrook W. C., Jr, Stead N. W., Pantazis C. G., Houston J. H., Crosby J. H. Embryonal rhabdomyosarcoma in ascitic fluid. Immunocytochemical and DNA flow cytometric study. Arch Pathol Lab Med. 1986 Sep;110(9):847–849. [PubMed] [Google Scholar]
  2. Auer G., Askensten U., Ahrens O. Cytophotometry. Hum Pathol. 1989 Jun;20(6):518–527. doi: 10.1016/0046-8177(89)90243-8. [DOI] [PubMed] [Google Scholar]
  3. Barlogie B., Raber M. N., Schumann J., Johnson T. S., Drewinko B., Swartzendruber D. E., Göhde W., Andreeff M., Freireich E. J. Flow cytometry in clinical cancer research. Cancer Res. 1983 Sep;43(9):3982–3997. [PubMed] [Google Scholar]
  4. Benjamin D. R. Proliferating cell nuclear antigen (PCNA) and pediatric tumors: assessment of proliferative activity. Pediatr Pathol. 1991 Jul-Aug;11(4):507–519. doi: 10.3109/15513819109064787. [DOI] [PubMed] [Google Scholar]
  5. Boyle E. T., Jr, Reiman H. M., Kramer S. A., Kelalis P. P., Rainwater L. M., Lieber M. M. Embryonal rhabdomyosarcoma of bladder and prostate: nuclear DNA patterns studied by flow cytometry. J Urol. 1988 Nov;140(5 Pt 2):1119–1121. doi: 10.1016/s0022-5347(17)41976-8. [DOI] [PubMed] [Google Scholar]
  6. Carlsen N. L., Ornvold K., Christensen I. J., Laursen H., Larsen J. K. Prognostic importance of DNA flow cytometrical, histopathological and immunohistochemical parameters in neuroblastomas. Virchows Arch A Pathol Anat Histopathol. 1992;420(5):411–418. doi: 10.1007/BF01600512. [DOI] [PubMed] [Google Scholar]
  7. Cattoretti G., Becker M. H., Key G., Duchrow M., Schlüter C., Galle J., Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992 Dec;168(4):357–363. doi: 10.1002/path.1711680404. [DOI] [PubMed] [Google Scholar]
  8. Clark G. M., Dressler L. G., Owens M. A., Pounds G., Oldaker T., McGuire W. L. Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med. 1989 Mar 9;320(10):627–633. doi: 10.1056/NEJM198903093201003. [DOI] [PubMed] [Google Scholar]
  9. Dressler L. G., Bartow S. A. DNA flow cytometry in solid tumors: practical aspects and clinical applications. Semin Diagn Pathol. 1989 Feb;6(1):55–82. [PubMed] [Google Scholar]
  10. Fox M. H., Armstrong L. W., Withrow S. J., Powers B. E., LaRue S. M., Straw R. C., Gillette E. L. Comparison of DNA aneuploidy of primary and metastatic spontaneous canine osteosarcomas. Cancer Res. 1990 Oct 1;50(19):6176–6178. [PubMed] [Google Scholar]
  11. Gansler T., Chatten J., Varello M., Bunin G. R., Atkinson B. Flow cytometric DNA analysis of neuroblastoma. Correlation with histology and clinical outcome. Cancer. 1986 Dec 1;58(11):2453–2458. doi: 10.1002/1097-0142(19861201)58:11<2453::aid-cncr2820581117>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Hedley D. W., Friedlander M. L., Taylor I. W., Rugg C. A., Musgrove E. A. Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem. 1983 Nov;31(11):1333–1335. doi: 10.1177/31.11.6619538. [DOI] [PubMed] [Google Scholar]
  14. Joensuu H., Kallioniemi O. P. Different opinions on classification of DNA histograms produced from paraffin-embedded tissue. Cytometry. 1989 Nov;10(6):711–717. doi: 10.1002/cyto.990100607. [DOI] [PubMed] [Google Scholar]
  15. Koss L. G., Czerniak B., Herz F., Wersto R. P. Flow cytometric measurements of DNA and other cell components in human tumors: a critical appraisal. Hum Pathol. 1989 Jun;20(6):528–548. doi: 10.1016/0046-8177(89)90244-x. [DOI] [PubMed] [Google Scholar]
  16. Kowal-Vern A., Gonzalez-Crussi F., Turner J., Trujillo Y. P., Chou P., Herman C., Castelli M., Walloch J. Flow and image cytometric DNA analysis in rhabdomyosarcoma. Cancer Res. 1990 Sep 15;50(18):6023–6027. [PubMed] [Google Scholar]
  17. Kowal-Vern A., Walloch J., Chou P., Gonzalez-Crussi F., Price J., Potocki D., Herman C. Flow and image cytometric DNA analysis in Ewing's sarcoma. Mod Pathol. 1992 Jan;5(1):56–60. [PubMed] [Google Scholar]
  18. Lawrence W., Jr, Gehan E. A., Hays D. M., Beltangady M., Maurer H. M. Prognostic significance of staging factors of the UICC staging system in childhood rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS-II). J Clin Oncol. 1987 Jan;5(1):46–54. doi: 10.1200/JCO.1987.5.1.46. [DOI] [PubMed] [Google Scholar]
  19. Ling V. Charles F. Kettering Prize. P-glycoprotein and resistance to anticancer drugs. Cancer. 1992 May 15;69(10):2603–2609. doi: 10.1002/1097-0142(19920515)69:10<2603::aid-cncr2820691034>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  20. Merkel D. E., Dressler L. G., McGuire W. L. Flow cytometry, cellular DNA content, and prognosis in human malignancy. J Clin Oncol. 1987 Oct;5(10):1690–1703. doi: 10.1200/JCO.1987.5.10.1690. [DOI] [PubMed] [Google Scholar]
  21. Molenaar W. M., Dam-Meiring A., Kamps W. A., Cornelisse C. J. DNA-aneuploidy in rhabdomyosarcomas as compared with other sarcomas of childhood and adolescence. Hum Pathol. 1988 May;19(5):573–579. doi: 10.1016/s0046-8177(88)80207-7. [DOI] [PubMed] [Google Scholar]
  22. Pedrick T. J., Donaldson S. S., Cox R. S. Rhabdomyosarcoma: the Stanford experience using a TNM staging system. J Clin Oncol. 1986 Mar;4(3):370–378. doi: 10.1200/JCO.1986.4.3.370. [DOI] [PubMed] [Google Scholar]
  23. Rodary C., Rey A., Olive D., Flamant F., Quintana E., Brunat-Mentigny M., Otten J., Voute P. A. Prognostic factors in 281 children with nonmetastatic rhabdomyosarcoma (RMS) at diagnosis. Med Pediatr Oncol. 1988;16(2):71–77. doi: 10.1002/mpo.2950160202. [DOI] [PubMed] [Google Scholar]
  24. Scrable H. J., Witte D. P., Lampkin B. C., Cavenee W. K. Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping. Nature. 1987 Oct 15;329(6140):645–647. doi: 10.1038/329645a0. [DOI] [PubMed] [Google Scholar]
  25. Shapiro D. N., Parham D. M., Douglass E. C., Ashmun R., Webber B. L., Newton W. A., Jr, Hancock M. L., Maurer H. M., Look A. T. Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma. J Clin Oncol. 1991 Jan;9(1):159–166. doi: 10.1200/JCO.1991.9.1.159. [DOI] [PubMed] [Google Scholar]
  26. Tsurusawa M., Katano N., Kawai S., Fujimoto T., Maeda M. Prognostic implication of cellular DNA content in acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol. 1988 Spring;10(1):75–80. doi: 10.1097/00043426-198821000-00013. [DOI] [PubMed] [Google Scholar]
  27. Van den Berg E., Molenaar W. M., Hoekstra H. J., Kamps W. A., de Jong B. DNA ploidy and karyotype in recurrent and metastatic soft tissue sarcomas. Mod Pathol. 1992 Sep;5(5):505–514. [PubMed] [Google Scholar]
  28. Wang-Wuu S., Soukup S., Ballard E., Gotwals B., Lampkin B. Chromosomal analysis of sixteen human rhabdomyosarcomas. Cancer Res. 1988 Feb 15;48(4):983–987. [PubMed] [Google Scholar]
  29. Wersto R. P., Liblit R. L., Koss L. G. Flow cytometric DNA analysis of human solid tumors: a review of the interpretation of DNA histograms. Hum Pathol. 1991 Nov;22(11):1085–1098. doi: 10.1016/0046-8177(91)90260-v. [DOI] [PubMed] [Google Scholar]
  30. van Thiel T. P., van der Linden J. C., Baak J. P., van de Sandt M. M., van Galen C., Bezemer P. D. Reproducibility of flow cytometric assessment of follicular tumours of the thyroid. J Clin Pathol. 1989 Mar;42(3):260–263. doi: 10.1136/jcp.42.3.260. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES