Yener AYTEKİN, Işın KILIÇARSLAN, Meral KOYUTÜRK

Evaluation of the proliferating activities of normal and carcinomatous prostatic tissues with Ki-67

Bu çalışmada, normal prostat dokusu, benign prostat hiperplazisi (BPH), prostatik intraepitelyal neoplazi (PIN) ve prostat kanseri doku örneklerinde proliferasyon aktivitesi immünohistokimyasal yöntemle Ki-67 monoklonal antikoru kullanılarak değerlendirildi. Ki-67, hücre siklusu boyunca eksprese edilen nükleer bir non-histon proteindir. Proliferasyon oranı, normal prostat glanduler epitelinde % 0.3-0.8 olarak, BPH de % 0.5-2.2, yüksek evreli PIN de % 1.6-3.7 ve prostat kanser vakalarında % 5-30 olarak bulundu. Proliferasyon aktiviteleri normal prostat dokusu ile karşılaştırıldığında BPH de hafif artış, PIN ve prostat kanserinde anlamlı yüksek artış gösterdi. Ki-67 proliferasyonndeksinin kanser grubunda Gleason sınıflandırmasıyla ilişkili olduğu bulundu. Ki-67 proliferasyon indeksinin değerli bir tam markın olarak PIN ve tümöral dokularda kullanılabileceği sonucuna varıldı.

Normal ve karsinomatöz prostat dokularının çoğalma aktivitelerinin Ki-67 ile değerlendirilmesi

In this study proliferation activities of normal prostate tissue, benign prostate hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostate cancer samples were evaluated immunohistochemically by using the monoclonal anti-Ki-67 antibody. Ki-67 is a nuclear non-histone protein expressed throughout the cell cycle. The proliferation rate was found to be 0.3-0.8 % in normal prostate glandular epithelium, 0.5-2.2 % in BPH, 1.6-3.7 % in high grade PIN and 5-30 % in prostate cancer cases. BPH showed a slightly higher, whereas PIN and prostate cancer showed significantly higher proliferation activity compared to normal prostate tissue. The Ki-67 proliferation index was found to correlate well with the Gleason classification in the cancer group. It is concluded that the Ki-67 proliferation index can be used a valuable diagnostic marker in PIN and tumor tissue.

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Bantis A, Giannopoulos A, Gonidi M, Liossi A, Aggelonidou E, Petrakakou E, Athanassiades P, and Athanassiadou P. Expression of p120, Ki- 67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value. Cytopathology. 15: 25-31, 2004.
Brown DC, Cole D, Gatter KC, and Mason DY. Carcinoma of the cervix uteri: an assessment of tumour proliferation using the monoclonal antibody Ki-67. Br J Cancer. 57: 178-181, 1988.
Brown DC, Gatter KC. Monoclonal antibody Ki-67: Its use in histopathology. Histopathology. 7: 489-503, 1990.
Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P, and Mihatsch MJ. Ki67 labelling index: An independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol. 178: 437-441, 1996.
Bubendorf L, Tapia C, Gasser TC, Casella R, Grunder B, Moch H, Mihatsch MJ, and Sauter G. Ki67 labelling index in core needle biopsies independently predicts tumor-specific survival in prostate cancer. Hum Pathol. 29: 949-954, 1998.
Claus S, Wrenger M, Senge T, and Schulze H. Immunohistochemical determination of age related proliferation rates in normal and benign hyperplastic human prostates. Urol Res. 21: 305-308, 1993.
Colombel M, Vacherot F, Diez SG, Fontaine E, Buttyan R, and Chopin D. Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia. Br J Urol. 82: 380-385, 1998.
Cowen D, Troncoso P, Khoo VS, Zagars GK, Von Eschenbach AC, Meistrich ML, and Pollack A. Ki-67 staining is an independent correlate of Biochemical Failure in prostate cancer treated with radiotherapy. Clin Cancer Res. 8: 1148-1154, 2002.
Feneley MR, Young MPA, Chinyema C, Kirby RS, and Parkinson MC. Ki-67 expression in early prostate cancer and associated pathological lesions. J Clin Pathol. 49: 741-748, 1996.
Gallee MPW, Jong EV, Kate F JNT, Schroeder FH, and Van der Kwast TH. Monoclonal antibody Ki-67 defined growth fraction in benign prostatic hyperplasia and prostatic cancer. J Urol. 142: 1342-1346, 1989.
Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, and Stein H. Cell cycle analysis of a cell proliferationassociated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 133: 1710-1715, 1984.
Gerdes J. An immunohistological method for estimating cell growth fractions in rapid histopathological diagnosis during surgery. Int J Cancer. 35: 169-171, 1985.
Gerdes J, Becker MH, Key G, and Cattoretti G. Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues. J Pathol. 168: 85-87, 1992.
Hall PA, Levison DA. Assessment of cell proliferation in histologic material. J Clin Pathol. 43: 184-192, 1990.
Hattori H. Sclerosing haemangioma of the lung is positive for MIB-1 in cell membrane and cytoplasmic staining pattern. Histopathology. 40: 291-293, 2002.
Jemal A, Tiwari RC., Murray T, Ghafoor A, Samuels A, Ward E,. Feuer EJ, and Thun MJ. Cancer Statistics, 2004. CA Cancer J Clin. 54: 8 – 29, 2004.
Key G, Becker MHG, Baron B, Duchrow M, Schluter C, Flad HD, and Gerdes J. New Ki-67 equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest. 68: 629-636,1993.
Leong AS, Wright J. The contribution of immunohistochemical staining in tumor diagnosis. Histopathology. 11: 1295-1305, 1987.
Mc Loughlin J, Foster CS, Price P, Williams G, and Abel PD. Evaluation of Ki-67 monoclonal antibody as prognostic indicator for prostatic carcinoma. Br J Urol. 72: 92-97, 1993.
Meyer JS, Sufrin G, Martin SA. Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling. J Urol. 128: 1353-1356, 1982.
Oxley JD, Abbott CD, Gillatt DA, and MacIver AG. Ductal carcinomas of the prostate: a clinicopathological and immunohistochemical study. Br J Urol. 81: 109-115,1998.
Sasaki K, Murakami T, Kawasaki M, and Takahashi M. The cell cycle associated change of the Ki-67 reactive nuclear antigen expression. J Cell Physiol. 133: 579-584, 1987.
Schonk DM, Kuijpers HJH, Van Drunen E, Van Dalen CH, Van Kessel AHG, Verheijen R, and Ramaekers FC. Assignment of the gene(s) involved in the exspression of the proliferation-related Ki-67 antigen to human chromosome 10. Hum Genet. 83: 297-299, 1989.
Shi SR, Key ME, Kalra KL. Antigen retrieval in formalinfixed, paraffin-embedded tissues: An enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 39: 741-747, 1991.
Stattin P, Damber J, Karlberg L, Tavelin B, and Damber JE. Cell proliferation assessed by Ki-67 immunoreactivity on formalin fixed tissues is a predictive factor for survival in prostate cancer. J Urol. 157: 219-222, 1997.
Tamboli P, Amin MB, Schultz DS, Linden MD, and Kubus J. Comparative analysis of the nuclear proliferative index (Ki-67) In benign prostate, prostatic intraepithelial neoplasia, and prostatic carcinoma. Mod Pathol. 9: 1015-1019, 1996.