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British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Jul;74(1):123–127. doi: 10.1038/bjc.1996.326

Heterogeneity in renal cell carcinoma and its impact no prognosis--a flow cytometric study.

B Ljungberg 1, C Mehle 1, R Stenling 1, G Roos 1
PMCID: PMC2074617  PMID: 8679445

Abstract

In the process of tumour progression genetic instability is the basis for the evolution of tumour cell clones with various genotypic and phenotypic characteristics causing heterogeneity. Renal cell carcinoma has a long prediagnostic growth period, which increases the probability of clonal evolution. We have studied 200 consecutive renal cell carcinomas, addressing the interrelationship between intratumour heterogeneity and clinicopathological factors. DNA ploidy patterns were analysed in multiple samples from each tumour using flow cytometry and compared with clinical stage, tumour invasion, metastatic rate and survival. Eighty-five of 192 evaluable tumours (44%) were homogeneous concerning DNA ploidy (62% diploid, 38% aneuploid). Among 107 heterogeneous tumours a majority (79%) contained aneuploid as well as diploid cell clones. Homogeneously diploid tumours had a lower incidence of local tumour spread compared with tumours with aneuploid cell clones (P < or = 0.001), but the frequency of distant metastasis at time of diagnosis was similar. The presence of aneuploidy in at least one sample from a tumour was a significant adverse prognostic factor (P < 0.001), whereas the degree of heterogeneity had no influence on survival. The frequent heterogeneity demonstrated indicates that multiple samples must be investigated to evaluate properly the malignant character of renal cell carcinoma.

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Selected References

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  1. Baretton G., Kuhlmann B., Krech R., Löhrs U. Intratumoural heterogeneity of nuclear DNA-content and proliferation in clear cell type carcinomas of the kidney. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61(1):57–63. doi: 10.1007/BF02890405. [DOI] [PubMed] [Google Scholar]
  2. Barranco S. C., Perry R. R., Durm M. E., Werner A. L., Gregorcyk S. G., Bolton W. E., Kolm P., Townsend C. M., Jr Intratumor variability in prognostic indicators may be the cause of conflicting estimates of patient survival and response to therapy. Cancer Res. 1994 Oct 15;54(20):5351–5356. [PubMed] [Google Scholar]
  3. Beerman H., Smit V. T., Kluin P. M., Bonsing B. A., Hermans J., Cornelisse C. J. Flow cytometric analysis of DNA stemline heterogeneity in primary and metastatic breast cancer. Cytometry. 1991;12(2):147–154. doi: 10.1002/cyto.990120208. [DOI] [PubMed] [Google Scholar]
  4. Bringuier P. P., Bouvier R., Berger N., Piaton E., Revillard J. P., Perrin P., Devonec M. DNA ploidy status and DNA content instability within single tumors in renal cell carcinoma. Cytometry. 1993;14(5):559–564. doi: 10.1002/cyto.990140516. [DOI] [PubMed] [Google Scholar]
  5. Fernö M., Baldetorp B., Ewers S. B., Idvall I., Olsson H., Sigurdsson H., Killander D. One or multiple samplings for flow cytometric DNA analyses in breast cancer-prognostic implications? Cytometry. 1992;13(3):241–249. doi: 10.1002/cyto.990130305. [DOI] [PubMed] [Google Scholar]
  6. Hiddemann W., Von Bassewitz D. B., Kleinemeier H. J., Schulte-Brochterbeck E., Hauss J., Lingemann B., Büchner T., Grundmann E. DNA stemline heterogeneity in colorectal cancer. Cancer. 1986 Jul 15;58(2):258–263. doi: 10.1002/1097-0142(19860715)58:2<258::aid-cncr2820580210>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  7. Larsson P., Roos G., Stenling R., Ljungberg B. Tumor-cell proliferation and prognosis in renal-cell carcinoma. Int J Cancer. 1993 Oct 21;55(4):566–570. doi: 10.1002/ijc.2910550408. [DOI] [PubMed] [Google Scholar]
  8. Ljungberg B., Larsson P., Roos G., Stenling R., Wilson G. Cell kinetics of renal cell carcinoma studied with in vivo iododeoxyuridine incorporation and flow cytometry. J Urol. 1994 Jun;151(6):1509–1513. doi: 10.1016/s0022-5347(17)35288-6. [DOI] [PubMed] [Google Scholar]
  9. Ljungberg B., Stenling R., Roos G. DNA content and prognosis in renal cell carcinoma. A comparison between primary tumors and metastases. Cancer. 1986 Jun 15;57(12):2346–2350. doi: 10.1002/1097-0142(19860615)57:12<2346::aid-cncr2820571218>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  10. Ljungberg B., Stenling R., Roos G. DNA content in renal cell carcinoma with reference to tumor heterogeneity. Cancer. 1985 Aug 1;56(3):503–508. doi: 10.1002/1097-0142(19850801)56:3<503::aid-cncr2820560316>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  11. Ljungberg B., Stenling R., Roos G. Tumor spread and DNA content in human renal cell carcinoma. Cancer Res. 1988 Jun 1;48(11):3165–3167. [PubMed] [Google Scholar]
  12. Masters J. R., Camplejohn R. S., Parkinson M. C., Woodhouse C. R., O'Reilly S. M. Does DNA flow cytometry give useful prognostic information in renal parenchymal adenocarcinoma? Br J Urol. 1992 Oct;70(4):364–369. doi: 10.1111/j.1464-410x.1992.tb15789.x. [DOI] [PubMed] [Google Scholar]
  13. Mehle C., Ljungberg B., Roos G. Telomere shortening in renal cell carcinoma. Cancer Res. 1994 Jan 1;54(1):236–241. [PubMed] [Google Scholar]
  14. Mehle C., Ljungberg B., Stenling R., Roos G. DNA fingerprinting of renal cell carcinoma with special reference to tumor heterogeneity. Genes Chromosomes Cancer. 1993 Feb;6(2):86–91. doi: 10.1002/gcc.2870060204. [DOI] [PubMed] [Google Scholar]
  15. Nicolson G. L. Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res. 1987 Mar 15;47(6):1473–1487. [PubMed] [Google Scholar]
  16. Nordenson I., Ljungberg B., Roos G. Chromosomes in renal carcinoma with reference to intratumor heterogeneity. Cancer Genet Cytogenet. 1988 May;32(1):35–41. doi: 10.1016/0165-4608(88)90309-3. [DOI] [PubMed] [Google Scholar]
  17. Norming U., Tribukait B., Gustafson H., Nyman C. R., Wang N. N., Wijkström H. Deoxyribonucleic acid profile and tumor progression in primary carcinoma in situ of the bladder: a study of 63 patients with grade 3 lesions. J Urol. 1992 Jan;147(1):11–15. doi: 10.1016/s0022-5347(17)37120-3. [DOI] [PubMed] [Google Scholar]
  18. Nowell P. C. Mechanisms of tumor progression. Cancer Res. 1986 May;46(5):2203–2207. [PubMed] [Google Scholar]
  19. Robson C. J., Churchill B. M., Anderson W. The results of radical nephrectomy for renal cell carcinoma. J Urol. 1969 Mar;101(3):297–301. doi: 10.1016/s0022-5347(17)62331-0. [DOI] [PubMed] [Google Scholar]
  20. Sasaki K., Hashimoto T., Kawachino K., Takahashi M. Intratumoral regional differences in DNA ploidy of gastrointestinal carcinomas. Cancer. 1988 Dec 15;62(12):2569–2575. doi: 10.1002/1097-0142(19881215)62:12<2569::aid-cncr2820621220>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  21. Sasaki K., Murakami T., Murakami T., Nakamura M. Intratumoral heterogeneity in DNA ploidy of esophageal squamous cell carcinomas. Cancer. 1991 Dec 1;68(11):2403–2406. doi: 10.1002/1097-0142(19911201)68:11<2403::aid-cncr2820681112>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  22. Skinner D. G., Colvin R. B., Vermillion C. D., Pfister R. C., Leadbetter W. F. Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer. 1971 Nov;28(5):1165–1177. doi: 10.1002/1097-0142(1971)28:5<1165::aid-cncr2820280513>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  23. Vogelstein B., Fearon E. R., Kern S. E., Hamilton S. R., Preisinger A. C., Nakamura Y., White R. Allelotype of colorectal carcinomas. Science. 1989 Apr 14;244(4901):207–211. doi: 10.1126/science.2565047. [DOI] [PubMed] [Google Scholar]

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