Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Oct;85(8):1119–1123. doi: 10.1054/bjoc.2001.2050

Sequential detection of alphafetoprotein-bearing cells in blood stem cell fraction of germ cell tumour patients

T Kasahara 1,2, N Hara 1, V Bilim 1, Y Tomita 1, K Saito 2, K Obara 2, K Takahashi 2
PMCID: PMC2375162  PMID: 11710823

Abstract

High-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation in advanced germ cell tumour (GCT) patients is widely applied. The aims of this study were: (1) To examine the presence of alphafetoprotein (AFP) bearing tumour cells in PBSC harvests from advanced GCT patients obtained after multiple cycles of induction chemotherapy. (2) To determine whether induction chemotherapy contributed to in vivo purging of the tumour. We evaluated cryopreserved PBSC samples from 5 patients with advanced stage II/III AFP producing GCT. PBSC were separated after the first, second and third cycles of induction chemotherapy. Those samples were analysed using the nested reverse transcription polymerase chain reaction (RT-PCR) method to detect AFP mRNA. Although, in all patients, AFP mRNA was detected in PBSC samples after the first or second cycle of induction chemotherapy, but was not detected in 3 of 4 samples after the third cycle of chemotherapy. Although it is not clear whether tumour cells contaminating PBSC fraction contribute to disease relapse, PBSC harvested after at least 3 cycles of induction chemotherapy might be recommended to avoid such a possibility. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Keywords: germ cell tumour, alphafetoprotein, peripheral blood stem cells, reverse transcription polymerase chain reaction

Full Text

The Full Text of this article is available as a PDF (64.5 KB).

Selected References

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

  1. Armitage J. O. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827–838. doi: 10.1056/NEJM199403243301206. [DOI] [PubMed] [Google Scholar]
  2. Beyer J., Kingreen D., Krause M., Schleicher J., Schwaner I., Schwella N., Huhn D., Siegert W. Long-term survival of patients with recurrent or refractory germ cell tumors after high dose chemotherapy. Cancer. 1997 Jan 1;79(1):161–168. [PubMed] [Google Scholar]
  3. Bilim V. N., Kawasaki T., Takahashi K., Tomita Y. Absence of frameshift mutations in the bax gene in renal cell cancer (RCC) and transitional cell cancer (TCC). Anticancer Res. 1998 May-Jun;18(3A):1655–1659. [PubMed] [Google Scholar]
  4. Brenner M. K., Rill D. R., Moen R. C., Krance R. A., Mirro J., Jr, Anderson W. F., Ihle J. N. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet. 1993 Jan 9;341(8837):85–86. doi: 10.1016/0140-6736(93)92560-g. [DOI] [PubMed] [Google Scholar]
  5. Broun E. R., Nichols C. R., Gize G., Cornetta K., Hromas R. A., Schacht B., Einhorn L. H. Tandem high dose chemotherapy with autologous bone marrow transplantation for initial relapse of testicular germ cell cancer. Cancer. 1997 Apr 15;79(8):1605–1610. doi: 10.1002/(sici)1097-0142(19970415)79:8<1605::aid-cncr25>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  6. Cooper B. W., Moss T. J., Ross A. A., Ybanez J., Lazarus H. M. Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer. J Clin Oncol. 1998 Nov;16(11):3509–3517. doi: 10.1200/JCO.1998.16.11.3509. [DOI] [PubMed] [Google Scholar]
  7. Craig J. I., Langlands K., Parker A. C., Anthony R. S. Molecular detection of tumor contamination in peripheral blood stem cell harvests. Exp Hematol. 1994 Aug;22(9):898–902. [PubMed] [Google Scholar]
  8. Elias A. D., Ayash L. J., Wheeler C., Schwartz G., Tepler I., Gonin R., McCauley M., Mazanet R., Schnipper L., Frei E., 3rd Phase I study of high-dose ifosfamide, carboplatin and etoposide with autologous hematopoietic stem cell support. Bone Marrow Transplant. 1995 Mar;15(3):373–379. [PubMed] [Google Scholar]
  9. Fan Y., Einhorn L., Saxman S., Katz B., Abonour R., Cornetta K. Detection of germ cell tumor cells in apheresis products using polymerase chain reaction. Clin Cancer Res. 1998 Jan;4(1):93–98. [PubMed] [Google Scholar]
  10. Fields K. K., Elfenbein G. J., Lazarus H. M., Cooper B. W., Perkins J. B., Creger R. J., Ballester O. F., Hiemenz J. H., Janssen W. E., Zorsky P. E. Maximum-tolerated doses of ifosfamide, carboplatin, and etoposide given over 6 days followed by autologous stem-cell rescue: toxicity profile. J Clin Oncol. 1995 Feb;13(2):323–332. doi: 10.1200/JCO.1995.13.2.323. [DOI] [PubMed] [Google Scholar]
  11. Fields K. K., Elfenbein G. J., Trudeau W. L., Perkins J. B., Janssen W. E., Moscinski L. C. Clinical significance of bone marrow metastases as detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplantation. J Clin Oncol. 1996 Jun;14(6):1868–1876. doi: 10.1200/JCO.1996.14.6.1868. [DOI] [PubMed] [Google Scholar]
  12. Ghossein R. A., Bhattacharya S., Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin Cancer Res. 1999 Aug;5(8):1950–1960. [PubMed] [Google Scholar]
  13. Gribben J. G., Freedman A. S., Neuberg D., Roy D. C., Blake K. W., Woo S. D., Grossbard M. L., Rabinowe S. N., Coral F., Freeman G. J. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med. 1991 Nov 28;325(22):1525–1533. doi: 10.1056/NEJM199111283252201. [DOI] [PubMed] [Google Scholar]
  14. Jiang S. Y., Shyu R. Y., Huang M. F., Tang H. S., Young T. H., Roffler S. R., Chiou Y. S., Yeh M. Y. Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis. Br J Cancer. 1997;75(6):928–933. doi: 10.1038/bjc.1997.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kennedy M. J., Vogelsang G. B., Jones R. J., Farmer E. R., Hess A. D., Altomonte V., Huelskamp A. M., Davidson N. E. Phase I trial of interferon gamma to potentiate cyclosporine-induced graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer. J Clin Oncol. 1994 Feb;12(2):249–257. doi: 10.1200/JCO.1994.12.2.249. [DOI] [PubMed] [Google Scholar]
  16. Knowles B. B., Howe C. C., Aden D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980 Jul 25;209(4455):497–499. doi: 10.1126/science.6248960. [DOI] [PubMed] [Google Scholar]
  17. Komeda T., Fukuda Y., Sando T., Kita R., Furukawa M., Nishida N., Amenomori M., Nakao K. Sensitive detection of circulating hepatocellular carcinoma cells in peripheral venous blood. Cancer. 1995 May 1;75(9):2214–2219. doi: 10.1002/1097-0142(19950501)75:9<2214::aid-cncr2820750905>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  18. Mapara M. Y., Körner I. J., Hildebrandt M., Bargou R., Krahl D., Reichardt P., Dörken B. Monitoring of tumor cell purging after highly efficient immunomagnetic selection of CD34 cells from leukapheresis products in breast cancer patients: comparison of immunocytochemical tumor cell staining and reverse transcriptase-polymerase chain reaction. Blood. 1997 Jan 1;89(1):337–344. [PubMed] [Google Scholar]
  19. Mattano L. A., Jr, Moss T. J., Emerson S. G. Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. Cancer Res. 1992 Sep 1;52(17):4701–4705. [PubMed] [Google Scholar]
  20. Morinaga T., Sakai M., Wegmann T. G., Tamaoki T. Primary structures of human alpha-fetoprotein and its mRNA. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4604–4608. doi: 10.1073/pnas.80.15.4604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moss T. J., Sanders D. G., Lasky L. C., Bostrom B. Contamination of peripheral blood stem cell harvests by circulating neuroblastoma cells. Blood. 1990 Nov 1;76(9):1879–1883. [PubMed] [Google Scholar]
  22. Nichols C. R., Andersen J., Lazarus H. M., Fisher H., Greer J., Stadtmauer E. A., Loehrer P. J., Trump D. L. High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol. J Clin Oncol. 1992 Apr;10(4):558–563. doi: 10.1200/JCO.1992.10.4.558. [DOI] [PubMed] [Google Scholar]
  23. Passos-Coelho J. L., Ross A. A., Kahn D. J., Moss T. J., Davis J. M., Huelskamp A. M., Noga S. J., Davidson N. E., Kennedy M. J. Similar breast cancer cell contamination of single-day peripheral-blood progenitor-cell collections obtained after priming with hematopoietic growth factor alone or after cyclophosphamide followed by growth factor. J Clin Oncol. 1996 Sep;14(9):2569–2575. doi: 10.1200/JCO.1996.14.9.2569. [DOI] [PubMed] [Google Scholar]
  24. Rill D. R., Santana V. M., Roberts W. M., Nilson T., Bowman L. C., Krance R. A., Heslop H. E., Moen R. C., Ihle J. N., Brenner M. K. Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells. Blood. 1994 Jul 15;84(2):380–383. [PubMed] [Google Scholar]
  25. Schulze R., Schulze M., Wischnik A., Ehnle S., Doukas K., Behr W., Ehret W., Schlimok G. Tumor cell contamination of peripheral blood stem cell transplants and bone marrow in high-risk breast cancer patients. Bone Marrow Transplant. 1997 Jun;19(12):1223–1228. doi: 10.1038/sj.bmt.1700817. [DOI] [PubMed] [Google Scholar]
  26. Spyridonidis A., Schmidt M., Bernhardt W., Papadimitriou A., Azemar M., Wels W., Groner B., Henschler R. Purging of mammary carcinoma cells during ex vivo culture of CD34+ hematopoietic progenitor cells with recombinant immunotoxins. Blood. 1998 Mar 1;91(5):1820–1827. [PubMed] [Google Scholar]
  27. Vannucchi A. M., Bosi A., Glinz S., Pacini P., Linari S., Saccardi R., Alterini R., Rigacci L., Guidi S., Lombardini L. Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT-PCR for cytokeratin-19 mRNA. Br J Haematol. 1998 Dec;103(3):610–617. doi: 10.1046/j.1365-2141.1998.01027.x. [DOI] [PubMed] [Google Scholar]
  28. Vogel W., Behringer D., Scheding S., Kanz L., Brugger W. Ex vivo expansion of CD34+ peripheral blood progenitor cells: implications for the expansion of contaminating epithelial tumor cells. Blood. 1996 Oct 1;88(7):2707–2713. [PubMed] [Google Scholar]
  29. Vredenburgh J. J., Silva O., Broadwater G., Berry D., DeSombre K., Tyer C., Petros W. P., Peters W. P., Bast R. C., Jr The significance of tumor contamination in the bone marrow from high-risk primary breast cancer patients treated with high-dose chemotherapy and hematopoietic support. Biol Blood Marrow Transplant. 1997 Jun;3(2):91–97. [PubMed] [Google Scholar]

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

RESOURCES