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Potential Role of bcl-2 and Ki-67 Expression and Apoptosis in Colorectal Carcinoma: A Clinicopathologic Study

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Abstract

Colorectal cancer is associated with deregulation of apoptotic and proliferative processes. The purpose of this study was to investigate the presence of apoptosis and proliferation in colorectal cancer and evaluate their possible correlation with classic prognostic markers and patients' survival. Tumors from 117 patients, followed for 44–142 months, were studied immunohistochemically using the anti-bcl-2 and anti-Ki-67 antibodies. Apoptotic body index (ABI) was assessed by a standard TUNEL method. The bcl-2 protein was detected in 65% of adenocarcinomas with increased expression in low-grade and early-stage tumors. No association was noted between bcl-2 expression and proliferative activity, ABI, or patients' survival. A positive correlation was observed between ABI and proliferation (P < 0.05). Apoptosis was more frequently observed in advanced tumor stage or high-grade neoplasms. Cox analysis revealed that only tumor stage and grade constituted independent prognostic factors. The study suggests that there is a possible deregulation of the mechanisms that control bcl-2 expression in high-grade and advanced-stage colorectal carcinomas. Regulation of apoptosis is a complex phenomenon and other factors, including tumor heterogeneity, may be involved.

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References

  1. Rosai J: Ackerman's Surgical Pathology, 8th ed, Vol. 1. St. Louis, Mosby, 1996

    Google Scholar 

  2. Bosman FT, Visser BC, van Oeveren J: Apoptosis: pathophysiology of programmed cell death. Pathol Res Pract 192:676-683, 1996

    Google Scholar 

  3. Cummings MC, Winterford CM, Walker NI: Apoptosis. Am J Surg Pathol 21:88-101, 1997

    Google Scholar 

  4. Staunton MJ, Gaffney EF: Apoptosis. Basic concepts and potential significance in human cancer. Arch Pathol Lab Med 122:310-319, 1998

    Google Scholar 

  5. Geske FJ, Gerschenson LE: The biology of apoptosis. Hum Pathol 32:1029-1038, 2001

    Google Scholar 

  6. Cleary ML, Sklar J: Nucleotide sequence of a t (14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a break-point cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci USA 82:7439-7443, 1985

    Google Scholar 

  7. Lu QL, Abel P, Foster CS, Lalani EN: Bcl-2: role in epithelial differentiation and oncogenesis. Hum Pathol 27:102-110, 1996

    Google Scholar 

  8. Krawejski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC: Investigations of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum and outer mitochondrial membranes. Cancer Res 53:4701-4714, 1993

    Google Scholar 

  9. Soini Y, Paakko P, Letho V-P: Histopathological evaluation of apoptosis in cancer. Am J Pathol 153:1041-1053, 1998

    Google Scholar 

  10. Scopa CD, Vagianos C, Kardamakis D, Kourelis TG, Kalofonos HP, Tsamandas AC: Bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with rectal cancer. Appl Immunohistochem Mol Morphol 9:329-334, 2001

    Google Scholar 

  11. Diebold J, Baretton G, Felchner M, Meier W, Dopfer K, Schmidt M, Lohrs U. Bcl-2 expression, p53 accumulation and apoptosis in ovarian carcinomas. Am J Clin Pathol 105:341-349, 1996

    Google Scholar 

  12. Pezzella F, Turley H, Kuzu I, Tungekar MF, Dunnill MS, Pietce CB, Harris A, Gatter KC, Mason DY: Bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med 329:690-694, 1993

    Google Scholar 

  13. Bubendorf L, Sauter G, Moch H, Jordan P, Blochlinger A, Gasser TC, Mihatsch MJ: Prognostic significance of bcl-2 in clinically localized prostate cancer. Am J Pathol 148:1557-1565, 1996

    Google Scholar 

  14. Saegusa M, Takano Y, Hashimura M, Okayasu I, Shiga J: The possible role of bcl-2 expression in the progression of tumors of the uterine cervix. Cancer 76:2297-2303, 1995

    Google Scholar 

  15. Karamitopoulou E, Perentes E, Tolnay M, Probst A: Prognostic significance of MIB-1, p53 and bcl-2 immunoreactivity in meningiomas. Hum Pathol 29:140-145, 1998

    Google Scholar 

  16. Koshida Y, Saegusa M, Okayasu I: Apoptosis, cell proliferation and expression of bcl-2 and bax in gastric carcinomas: immunohistochemical and clinicopathological study. Br J Cancer 75:367-373, 1997

    Google Scholar 

  17. Scopa CD, Vagianos C, Kourelis T, Tsamandas AC: The potential role of bcl—2, p53 and bax expression in rectal adenocarcinoma and their correlation with tumor prognosis. Eur Surg Res 32(suppl 1):7, 2000

    Google Scholar 

  18. Kaklamanis L, Savage A, Whitehouse R, Doussis-Anagnostopoulou I, Biddolph S, Tsiotos P, Mortensen N, Gatter KC, Harris AL: Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer. Br J Cancer 77:1864-1869, 1998

    Google Scholar 

  19. Sinicrope FA, Hart J, Michelassi F, Lee JJ: Prognostic value of bcl-2 oncoprotein expression in stage II colon carcinoma. Clin Cancer Res 1:1103-1110, 1995

    Google Scholar 

  20. Scott RJ, Hall PA, Haldane JS, van Noorden S, Price Y, Lane DP, Wright NA: A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction. J Pathol 165:173-178, 1991

    Google Scholar 

  21. Kruger S, Muller H: Correlation of morphometry, nucleolar organizer regions, proliferating cell nuclear antigen and Ki-67 antigen expression with grading and staging in urinary bladder carcinomas. Br J Urol 75:480-484, 1995

    Google Scholar 

  22. Jass JR, Sobin LH: Histological Typing of Intestinal Tumors: World Health Organization, 2nd ed. New York, Springer-Verlag, 1989

    Google Scholar 

  23. Saleh HA, Jackson H, Khatib G, Banerjee M: Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia. Pathol Oncol Res 5:273-279, 1999

    Google Scholar 

  24. Bosari S, Moneghini L, Graziani D, Lee AK, Murray JJ, Coggi G, Viale G: Bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas and adenocarcinomas. Hum Pathol 26:534-540, 1995

    Google Scholar 

  25. Nakamura T, Nomura S, Sakai T, Nariya S: Expression of bcl-2 oncoprotein in gastrointestinal and uterine carcinomas and their premalignant lesions. Hum Pathol 28:309-315, 1997

    Google Scholar 

  26. Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ: Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci USA 88:6961-6965, 1991

    Google Scholar 

  27. Stewart BW: Mechanism of apoptosis: integration of genetic, biochemical and cellular indications. J Natl Cancer Inst 86:1286-1298, 1994

    Google Scholar 

  28. Miyashita T, Reed JC: Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799-1805, 1994

    Google Scholar 

  29. Haldar S, Negrini M, Monne M, Sabbioni S, Crose CM: Down-regulation of bcl-2 by p53 in breast cancer cells. Cancer Res 54:2095-2097, 1994

    Google Scholar 

  30. Boise LH, Gonzales-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB: Bcl-x, a bcl-2 related gene that functions as a dominant regulator of apoptotic cell death. Cell 74:597-608, 1993

    Google Scholar 

  31. Oltvai ZN, Milliman CL, Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homologue BAX that accelerates cell death. Cell 74:609-619, 1993

    Google Scholar 

  32. Manne U, Myers RB, Moron C, Poczatek RB, Dillard S, Weiss H, Brown D, Stivastava S, Grizzle WE: Prognostic significance of bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer 74:346-358, 1997

    Google Scholar 

  33. Bhatavdekar JM, Patel DD, Ghosh N, Chikhlikar PR, Trivedi TI, Suthar TP, Doctor SS, Shah NG, Balar DB: Co-expression of bcl-2, c-Myc and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma. Dis Colon Rectum 40:785-590, 1997

    Google Scholar 

  34. Giatromanolaki A, Stathopoulos GP, Tsiobanou E, Papadimitriou C, Georgoulias V, Gatter KC, Bizakis JG, Retalis G, Karkavitsas N, Helidonis ES: Combined role of tumor angiogenesis, bcl-2 and p53 expression in the prognosis of patients with colorectal carcinoma. Cancer 86:1421-1430, 1999

    Google Scholar 

  35. Tollenaar RA, van Krieken JH, van Slooten HJ, Bruinvels DJ, Nelemans KM, van den Broek LJ, Hermans J, van Dierendonk JH: Immunohistochemical detection of p53 and bcl-2 in colorectal carcinoma: no evidence for prognostic significance. Br J Cancer 77:1842-1847, 1998

    Google Scholar 

  36. Doglioni C, Dei Tos AP, Laurino L, Chiarelli C, Barbareschi M, Viale C: The prevalence of bcl-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to estrogen receptor status. Virchows Arch 424:47-51, 1994

    Google Scholar 

  37. Saegusa M, Takano Y, Okayasu I: Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia. J Cancer Res Clin Oncol 121:357-363, 1995

    Google Scholar 

  38. Tabete S, Ishida M, Kasagi N, Tsujitanis S, Kaibara N, Ito H: Apoptosis occurs more frequent in metastatic foci than in primary lesions of human colorectal carcinomas: analysis by terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling. Int J Cancer 65:173-177, 1996

    Google Scholar 

  39. Takano Y, Saegusa M, Ikenaga M, Mitomi H, Okayasu I: Apoptosis in colon cancer: comparison with Ki-67 proliferative activity and expression of p53. J Cancer Res Clin Oncol 122:166-170, 1996

    Google Scholar 

  40. Ioffe OB, Papadimitriou JC, Drachenberg CB: Correlation of proliferation indices, apoptosis and related oncogene expression (bcl-2 and c-erbB-2) and p53 in proliferative, hyperplastic and malignant endometrium. Hum Pathol 29:1150-1159, 1998

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Rion University Hospital, University of Patras, Medical School, Patras, Greece

    Chrisoula D. Scopa, Athanassios C. Tsamandas, Vicky Zolota & Anna Batistatou

  2. Department of Medical Oncology, Rion University Hospital, University of Patras, Medical School, Patras, Greece

    Haralabos P. Kalofonos

  3. Department of Surgery, Rion University Hospital, University of Patras, Medical School, Patras, Greece

    Constantine Vagianos

Authors
  1. Chrisoula D. Scopa
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  2. Athanassios C. Tsamandas
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  3. Vicky Zolota
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  5. Anna Batistatou
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  6. Constantine Vagianos
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Scopa, C.D., Tsamandas, A.C., Zolota, V. et al. Potential Role of bcl-2 and Ki-67 Expression and Apoptosis in Colorectal Carcinoma: A Clinicopathologic Study. Dig Dis Sci 48, 1990–1997 (2003). https://doi.org/10.1023/A:1026178506348

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  • DOI: https://doi.org/10.1023/A:1026178506348