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. 1999 Dec;52(6):341–344. doi: 10.1136/mp.52.6.341

Abl expression, tumour grade, and apoptosis in chondrosarcoma.

M O'Donovan 1, J M Russell 1, J J O'Leary 1, J A Gillan 1, M P Lawler 1, E F Gaffney 1
PMCID: PMC395719  PMID: 10748867

Abstract

AIMS: To determine whether Abl immunoreactivity correlates with grade and cell kinetics (apoptosis and mitosis) in chondrosarcoma. METHODS: Sections from 16 chondrosarcomas were stained immunohistochemically using a polyclonal antibody to the c-Abl/Bcr-Abl oncoprotein. Apoptotic indices and mitotic indices were assessed in all tumours. Sections from 24 paraffin wax blocks of human fetal rib (gestational ages, 15-42 weeks) were also stained to determine whether the Abl protein is synthesised consistently throughout endochondral ossification. RESULTS: Abl staining in immature fetal rib chondrocytes at all stages of development was predominantly nuclear, and 70% of cells showed moderate to strong staining. Abl immunoreactivity was minimal or absent in hypertrophic chondrocytes about to undergo apoptosis at the growth plate. There was strong Abl staining in grade 1 and grade 2 chondrosarcomas but staining was greatly reduced or absent in grade 3 chondrosarcomas. There was a very significant linear correlation between apoptotic index (mean, 0.68%; range, 0-3.2%) and mitotic index (mean, 0.23%; range, 0-0.9%), and both indices were significantly lower in grade 1 than in grade 2 and grade 3 chondrosarcomas. CONCLUSIONS: These data suggest that abl gene expression is associated with differentiation and apoptosis inhibition in fetal and neoplastic chondrocytes. However, these putative effects cannot be ascribed solely to the Abl protein, because several additional factors contribute to the regulation of both differentiation and apoptosis.

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Selected References

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  1. Bedi A., Zehnbauer B. A., Barber J. P., Sharkis S. J., Jones R. J. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood. 1994 Apr 15;83(8):2038–2044. [PubMed] [Google Scholar]
  2. Björnsson J., McLeod R. A., Unni K. K., Ilstrup D. M., Pritchard D. J. Primary chondrosarcoma of long bones and limb girdles. Cancer. 1998 Nov 15;83(10):2105–2119. [PubMed] [Google Scholar]
  3. Chung S. W., Daniel R., Wong B. Y., Wong P. M. The ABL genes in normal and abnormal cell development. Crit Rev Oncog. 1996;7(1-2):33–48. doi: 10.1615/critrevoncog.v7.i1-2.30. [DOI] [PubMed] [Google Scholar]
  4. Daniel R., Wong P. M., Chung S. W. Isoform-specific functions of c-abl: type I is necessary for differentiation, and type IV is inhibitory to apoptosis. Cell Growth Differ. 1996 Sep;7(9):1141–1148. [PubMed] [Google Scholar]
  5. Enomoto-Iwamoto M., Iwamoto M., Mukudai Y., Kawakami Y., Nohno T., Higuchi Y., Takemoto S., Ohuchi H., Noji S., Kurisu K. Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes. J Cell Biol. 1998 Jan 26;140(2):409–418. doi: 10.1083/jcb.140.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evan G., Littlewood T. A matter of life and cell death. Science. 1998 Aug 28;281(5381):1317–1322. doi: 10.1126/science.281.5381.1317. [DOI] [PubMed] [Google Scholar]
  7. Farnum C. E., Turgai J., Wilsman N. J. Visualization of living terminal hypertrophic chondrocytes of growth plate cartilage in situ by differential interference contrast microscopy and time-lapse cinematography. J Orthop Res. 1990 Sep;8(5):750–763. doi: 10.1002/jor.1100080517. [DOI] [PubMed] [Google Scholar]
  8. Farnum C. E., Wilsman N. J. Morphologic stages of the terminal hypertrophic chondrocyte of growth plate cartilage. Anat Rec. 1987 Nov;219(3):221–232. doi: 10.1002/ar.1092190303. [DOI] [PubMed] [Google Scholar]
  9. Gibson G. J., Kohler W. J., Schaffler M. B. Chondrocyte apoptosis in endochondral ossification of chick sterna. Dev Dyn. 1995 Aug;203(4):468–476. doi: 10.1002/aja.1002030409. [DOI] [PubMed] [Google Scholar]
  10. Gibson G., Lin D. L., Roque M. Apoptosis of terminally differentiated chondrocytes in culture. Exp Cell Res. 1997 Jun 15;233(2):372–382. doi: 10.1006/excr.1997.3576. [DOI] [PubMed] [Google Scholar]
  11. Hasegawa T., Seki K., Yang P., Hirose T., Hizawa K., Wada T., Wakabayashi J. Differentiation and proliferative activity in benign and malignant cartilage tumors of bone. Hum Pathol. 1995 Aug;26(8):838–845. doi: 10.1016/0046-8177(95)90004-7. [DOI] [PubMed] [Google Scholar]
  12. Kameda T., Watanabe H., Iba H. C-Jun and JunD suppress maturation of chondrocytes. Cell Growth Differ. 1997 May;8(5):495–503. [PubMed] [Google Scholar]
  13. Kennedy M. M., Lucas S. B., Russell-Jones R., Howells D. D., Picton S. J., Bardon A., Comley I. L., McGee J. O., O'Leary J. J. HHV8 and female Kaposi's sarcoma. J Pathol. 1997 Dec;183(4):447–452. doi: 10.1002/(SICI)1096-9896(199712)183:4<447::AID-PATH954>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  14. Leoncini L., Del Vecchio M. T., Megha T., Barbini P., Galieni P., Pileri S., Sabattini E., Gherlinzoni F., Tosi P., Kraft R. Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas. Am J Pathol. 1993 Mar;142(3):755–763. [PMC free article] [PubMed] [Google Scholar]
  15. Lipponen P. K., Aaltomaa S. Apoptosis in bladder cancer as related to standard prognostic factors and prognosis. J Pathol. 1994 Aug;173(4):333–339. doi: 10.1002/path.1711730408. [DOI] [PubMed] [Google Scholar]
  16. McGahon A. J., Cotter T. G., Green D. R. The abl oncogene family and apoptosis. Cell Death Differ. 1994;1(2):77–83. [PubMed] [Google Scholar]
  17. McMenamin M. E., O'Neill A. J., Gaffney E. F. Extent of apoptosis in ovarian serous carcinoma: relation to mitotic and proliferative indices, p53 expression, and survival. Mol Pathol. 1997 Oct;50(5):242–246. doi: 10.1136/mp.50.5.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. O'Neill A. J., Cotter T. G., Russell J. M., Gaffney E. F. Abl expression in human fetal and adult tissues, tumours, and tumour microvessels. J Pathol. 1997 Nov;183(3):325–329. doi: 10.1002/(SICI)1096-9896(199711)183:3<325::AID-PATH941>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  19. O'Neill A. J., Staunton M. J., Gaffney E. F. Apoptosis occurs independently of bcl-2 and p53 over-expression in non-small cell lung carcinoma. Histopathology. 1996 Jul;29(1):45–50. doi: 10.1046/j.1365-2559.1996.d01-478.x. [DOI] [PubMed] [Google Scholar]
  20. Roach H. I., Erenpreisa J., Aigner T. Osteogenic differentiation of hypertrophic chondrocytes involves asymmetric cell divisions and apoptosis. J Cell Biol. 1995 Oct;131(2):483–494. doi: 10.1083/jcb.131.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sawyers C. L., McLaughlin J., Goga A., Havlik M., Witte O. The nuclear tyrosine kinase c-Abl negatively regulates cell growth. Cell. 1994 Apr 8;77(1):121–131. doi: 10.1016/0092-8674(94)90240-2. [DOI] [PubMed] [Google Scholar]
  22. Staunton M. J., Gaffney E. F. Apoptosis: basic concepts and potential significance in human cancer. Arch Pathol Lab Med. 1998 Apr;122(4):310–319. [PubMed] [Google Scholar]
  23. Staunton M. J., Gaffney E. F. Tumor type is a determinant of susceptibility to apoptosis. Am J Clin Pathol. 1995 Mar;103(3):300–307. doi: 10.1093/ajcp/103.3.300. [DOI] [PubMed] [Google Scholar]
  24. Taagepera S., McDonald D., Loeb J. E., Whitaker L. L., McElroy A. K., Wang J. Y., Hope T. J. Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7457–7462. doi: 10.1073/pnas.95.13.7457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wang J. Y. Abl tyrosine kinase in signal transduction and cell-cycle regulation. Curr Opin Genet Dev. 1993 Feb;3(1):35–43. doi: 10.1016/s0959-437x(05)80338-7. [DOI] [PubMed] [Google Scholar]
  26. Wen S. T., Jackson P. K., Van Etten R. A. The cytostatic function of c-Abl is controlled by multiple nuclear localization signals and requires the p53 and Rb tumor suppressor gene products. EMBO J. 1996 Apr 1;15(7):1583–1595. [PMC free article] [PubMed] [Google Scholar]
  27. Yang C., Li S. W., Helminen H. J., Khillan J. S., Bao Y., Prockop D. J. Apoptosis of chondrocytes in transgenic mice lacking collagen II. Exp Cell Res. 1997 Sep 15;235(2):370–373. doi: 10.1006/excr.1997.3692. [DOI] [PubMed] [Google Scholar]
  28. Zenmyo M., Komiya S., Kawabata R., Sasaguri Y., Inoue A., Morimatsu M. Morphological and biochemical evidence for apoptosis in the terminal hypertrophic chondrocytes of the growth plate. J Pathol. 1996 Dec;180(4):430–433. doi: 10.1002/(SICI)1096-9896(199612)180:4<430::AID-PATH691>3.0.CO;2-H. [DOI] [PubMed] [Google Scholar]

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