Abstract
Aim—To investigate whether clinical features of non-Hodgkin's lymphomas, at the time of first biopsy, correlate with studies of cell proliferation and cell death as well as with the level of bcl-2 expression.
Methods—Bcl-2 expression, determined by immunocytochemistry, was compared with cell proliferation, measured using in situ hybridisation for histone mRNA, and cell death by apoptosis, measured using in situ end labelling for DNA cleavage.
Results—Histone mRNA staining gave a labelling index of 30% of cells for reactive germinal centres, 5.2-13.5% of cells for low grade non-Hodgkin's lymphoma and 12.1-50.5% of cells for high grade non-Hodgkin's lymphoma. In situ end labelling gave a labelling index of 5.0-10.0% of cells for reactive germinal centres, 1.0-3.7% of cells for low grade non-Hodgkin's lymphoma and 4.7-13.5% of cells for high grade non-Hodgkin's lymphoma. There was a positive correlation between apoptotic index and proliferation index. More cases of low grade than high grade non-Hodgkin's lymphoma expressed bcl-2. There was no correlation between apoptotic index and bcl-2 expression for high grade non-Hodgkin's lymphoma.
Conclusions—The molecular mechanisms controlling cell proliferation and death in non-Hodgkin's lymphoma are complex, probably involving a range of genes, including bcl-2. A better understanding of resistance to cell death is needed if the clinical goal of tailoring cancer treatment to individual tumours is to be achieved.
Keywords: non-Hodgkin's lymphoma
Keywords: apoptosis
Keywords: proliferation
Keywords: bcl-2
Keywords: grade
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- Alison M., Chaudry Z., Baker J., Lauder I., Pringle H. Liver regeneration: a comparison of in situ hybridization for histone mRNA with bromodeoxyuridine labeling for the detection of S-phase cells. J Histochem Cytochem. 1994 Dec;42(12):1603–1608. doi: 10.1177/42.12.7983360. [DOI] [PubMed] [Google Scholar]
- Ansari B., Coates P. J., Greenstein B. D., Hall P. A. In situ end-labelling detects DNA strand breaks in apoptosis and other physiological and pathological states. J Pathol. 1993 May;170(1):1–8. doi: 10.1002/path.1711700102. [DOI] [PubMed] [Google Scholar]
- Bakhshi A., Jensen J. P., Goldman P., Wright J. J., McBride O. W., Epstein A. L., Korsmeyer S. J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. doi: 10.1016/s0092-8674(85)80070-2. [DOI] [PubMed] [Google Scholar]
- Cattoretti G., Pileri S., Parravicini C., Becker M. H., Poggi S., Bifulco C., Key G., D'Amato L., Sabattini E., Feudale E. Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections. J Pathol. 1993 Oct;171(2):83–98. doi: 10.1002/path.1711710205. [DOI] [PubMed] [Google Scholar]
- Du M., Singh N., Husseuin A., Isaacson P. G., Pan L. Positive correlation between apoptotic and proliferative indices in gastrointestinal lymphomas of mucosa-associated lymphoid tissue (MALT). J Pathol. 1996 Apr;178(4):379–384. doi: 10.1002/(SICI)1096-9896(199604)178:4<379::AID-PATH487>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
- Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gratzner H. G. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science. 1982 Oct 29;218(4571):474–475. doi: 10.1126/science.7123245. [DOI] [PubMed] [Google Scholar]
- Hermine O., Haioun C., Lepage E., d'Agay M. F., Briere J., Lavignac C., Fillet G., Salles G., Marolleau J. P., Diebold J. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 1996 Jan 1;87(1):265–272. [PubMed] [Google Scholar]
- Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
- Korsmeyer S. J. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992 Aug 15;80(4):879–886. [PubMed] [Google Scholar]
- 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]
- Quinn C. M., Wright N. A. The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol. 1990 Feb;160(2):93–102. doi: 10.1002/path.1711600202. [DOI] [PubMed] [Google Scholar]
- Tsujimoto Y., Finger L. R., Yunis J., Nowell P. C., Croce C. M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984 Nov 30;226(4678):1097–1099. doi: 10.1126/science.6093263. [DOI] [PubMed] [Google Scholar]
- Zutter M., Hockenbery D., Silverman G. A., Korsmeyer S. J. Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms. Blood. 1991 Aug 15;78(4):1062–1068. [PubMed] [Google Scholar]
- del Vecchio M. T., Leoncini L., Buerki K., Kraft R., Megha T., Barbini P., Tosi P., Cottier H. Diffuse centrocytic and/or centroblastic malignant non-Hodgkin's lymphomas: comparison of mitotic and pyknotic (apoptotic) indices. Int J Cancer. 1991 Jan 2;47(1):38–43. doi: 10.1002/ijc.2910470108. [DOI] [PubMed] [Google Scholar]


