Abstract
To assess cell death and cellular proliferation activity, the apoptosis index, the Ki67 proliferative index and overexpression of p53 protein were evaluated in 69 oesophageal squamous cell carcinomas (ESCC), all surgically resected from Japanese patients. Apoptosis was examined by Gavrieli's method in histological sections, and proved to be significantly related to keratinization and ESCC progression. Overall labelling indices were 15.68±4.04 (positive/1,000 nuclei) and 6.79±0.64 respectively, in keratinizing and nonkeratinizing types. The apoptosis labelling index increased, especially in keratinizing lesions, from 4.50±0.59 with cancer invasion to mucosa through 11.46±2.70 with involvement of the submucosa up to 21.18±3.72 in cases of penetration to the muscularis propria or adventitia. The relationship between apoptosis, Ki67 scores and p53 expression was determined in identical cancer nests on serial sections. An inverse correlation was shown between the apoptosis score and the Ki67 score in both keratinizing and nonkeratinizing types. There was no significant correlation between apoptosis score and p53 expression, either overall or separately in keratinizing or nonkeratinizing types of ESCC. Our results suggest that a mechanism of induction of apoptosis similar to that operating in normal epidermis acts in keratinizing ESCC, and that as tumour volume increases, single cell death becomes more frequent.
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Aihara M, Truong LD, Dunn JK, Wheeler TM, Scardino PT, Thompson TC (1994) Frequency of apoptotic bodies positively correlates with Gleason grade in prostate cancer. Hum Pathol 25: 797–801
Bellomo G, Perotti M, Taddei F, Mirabelli F, Finardi G, Nicotera P, et al (1992) Tumour necrosis factor-α induces apoptosis in mammary adenocarcinoma cells by an increase in intracellular free Ca2+ concentration and DNA fragmentation. Cancer Res 52: 1342–1346
Curson C, Weedon D (1979) Spontaneous regression in basal cell carcinomas. J Cutan Pathol 6: 432–437
D'Errico A, Grigioni WF, Fiorentino M, Baccarini P, Grazi GL, Mancini AM (1994) Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma: an immunohistochemical study on 109 Italian patients. Pathol Int 44: 682–687
Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M (1989) Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci USA 86: 8763–8767
El-Labban NG, Osorio-Herrera E (1986) Apoptotic bodies and abnormally dividing epithelial cells in squamous cell carcinoma. Histopathology 10: 921–931
Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493–501
Gerdes J, Schwab U, Lemke H, Stein H (1982) Production of mouse monoclonal antibody reaction with a human nuclear antigen associated with cell proliferation. Int J Cancer 31: 13–20
Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by monoclonal antibody. J Immunol 133: 1710–1715
Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253: 49–53
Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239–257
Kerr JFR, Winterford CM, Harmon BV (1994) Apoptosis: its significance in cancer and cancer therapy. Cancer 73: 2013–2026
Lane DP (1993) A death in the life of p53. Nature 362: 786–787
Leoncini L, Vecchio MTD, Megha T, Barbini P, Galieni P, Pileri S, Sabattini E, Gherlinzoni F, Tosi P, Kraft R, Cottier H (1993) Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas. Am J Pathol 142: 755–763
Levine AJ, Momand J, Finlay CA (1991) The p53 tumor suppressor gene. Nature 351: 453–456
McCall CA, Cohen JJ (1991) Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease. J Invest Dermatol 97: 111–114
Milner J (1991) The role of p53 in the normal control of cell population. Curr Opin Cell Biol 3: 282–286
Searle J, Collins DJ, Harmon B, Kerr JFR (1973) The spontaneous occurence of apoptosis in squamous carcinoma of the uterine cervix. Pathology 5: 163–169
Wagata T, Shibagaki I, Imamura M, Shimada Y, Toguchida J, Yandell DW, Ikenaga M, Tobe T, Ishizaki K (1993) Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res 53: 846–850
Wright SC, Kumar P, Tam AW, Shen N, Varma M, Larrick JW (1992) Apoptosis and DNA fragmentation precede TNF-induced cytolysis in U937 cells. J Cell Biochem 48: 344–355
Wyllie AH (1985) The biology of cell death in tumors. Anticancer Res 5: 131–136
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Ohbu, M., Saegusa, M. & Okayasu, I. Apoptosis and cellular proliferation in oesophageal squamous cell carcinomas: differences between keratinizing and nonkeratinizing types. Vichows Archiv A Pathol Anat 427, 271–276 (1995). https://doi.org/10.1007/BF00203394
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DOI: https://doi.org/10.1007/BF00203394