ANALYSIS OF APOPTOTIC CELLS IN SURGICAL PATHOLOGY MATERIALS

Analysis of tissue turnover, the balance between cell proliferation and cell death, can provide important information about our understanding of the biological characteristics of various tissues and their functions. Especially it is very important to study apoptosis, one of the modes of cell death, in surgical pathology specimens. It is very important to note that the whole concept of cell death including apoptosis and oncosis is based on the morphological findings. Therefore, an analysis of morphological features of the cells undergoing the processes of various modes of cell death is very important. DNA fragmentation can be detected in situ by labeling 3′-OH ends with biotinylated deoxyuridine triphosphate (dUTP) through the action of terminal deoxynucleotidyl transferase (TdT).Since then, this method, subsequently termed 3′-OH nick end labeling, or TdT-mediated dUTP-biotin nick end labeling (TUNEL), has been widely used to detect cells with DNA fragmentation, especially in surgical pathology materials of human disorders. This TUNEL method is now being incorporated into many pathology laboratories throughout the world. However, increasing evidence suggest that TUNEL method is by no means specific for the detection of apoptosis and this method may also detect cells which are committed to, but not yet in the process of apoptosis. Therefore, it is very important to correlate the findings of TUNEL with morphological features of surgical pathology specimens. In addition, it is also important to note that over-fixation is associated with false negative results and insufficient fixation is likely to be associated with false positive results. Therefore, the processing of the specimens including fixation and others is critical in performing TUNEL and its interpretation.

[1]  H. Sasano,et al.  Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats. , 1998, Gastroenterology.

[2]  H. Sasano,et al.  Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma. , 1997, The American journal of pathology.

[3]  H. Sasano,et al.  Ultrastructural and confocal laser scanning microscopic examination of TUNEL‐positive cells , 1997, The Journal of pathology.

[4]  T. Shimosegawa,et al.  The role of endogenous glucocorticoids in rat experimental models of acute pancreatitis. , 1995, Gastroenterology.

[5]  H. Sasano In situ end labeling and its applications to the study of endocrine disease: How can we study programmed cell death in surgical pathology materials? , 1995 .

[6]  S. Hakomori,et al.  Ley antigen expression is correlated with apoptosis (programmed cell death) , 1993 .

[7]  P. Hall,et al.  In situ end‐labelling detects DNA strand breaks in apoptosis and other physiological and pathological states , 1993, The Journal of pathology.

[8]  R. S. Sloviter,et al.  Adrenalectomy‐induced granule cell degeneration in the rat hippocampal dentate gyrus: Characterization of an in vivo model of controlled neuronal death , 1993, The Journal of comparative neurology.

[9]  A. Wyllie,et al.  Apoptosis (the 1992 Frank Rose Memorial Lecture). , 1993, British Journal of Cancer.

[10]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[11]  Gwyn T. Williams,et al.  Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures , 1989, Nature.

[12]  N. Kyprianou,et al.  Activation of programmed cell death in the rat ventral prostate after castration. , 1988, Endocrinology.

[13]  A. Wyllie,et al.  Death and the cell. , 1986, Immunology today.

[14]  A. Wyllie,et al.  Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis , 1984, The Journal of pathology.

[15]  A. Wyllie Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation , 1980, Nature.

[16]  A. Wyllie,et al.  Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics , 1972, British Journal of Cancer.

[17]  G. Majno,et al.  Apoptosis, oncosis, and necrosis. An overview of cell death. , 1995, The American journal of pathology.

[18]  H. Ohyama,et al.  Radiation-induced interphase death of rat thymocytes is internally programmed (apoptosis). , 1988, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[19]  A. Wyllie Cell death: a new classification separating apoptosis from necrosis , 1981 .

[20]  A. Wyllie,et al.  Cell death: the significance of apoptosis. , 1980, International review of cytology.