PROGNOSTIC SIGNIFICANCE OF Ki-67, P53 IN PATIENTS WITH PROSTATE CANCER AND THEIR CORRELATION WITH STANDARD INDICATORS
Background: Prostate cancer is currently one of the most socially significant cancers in the world. In the United States and some European countries in terms of incidence of prostate cancer came in the first place in the structure of cancer pathology in men [2]. Up to 40% of men aged 60 to 70 years and 70% of men over 80 years have different stages of prostate cancer. More than 50% of patients go to a doctor with an already advanced disease in the T3-T4 stage and with metastases [3].
The last decade has been marked by the search for new methods of diagnosis of prostate cancer that can provide a more accurate assessment of its outcomes and minimizite the negative effects and maximize the positive impact of existing treatments. The most active direction of scientific research is the study of associated molecular biological markers characterizing the processes of proliferation, apoptosis and neoangiogenesis of tumor tissue.
However, molecular biological markers have not yet found their place in the daily practice of a oncourologist due to insufficient data on their impact on treatment outcomes.
Aim: The aim of this study was to study the clinical significance of the expression of immunohistochemical markers (Ki67, P53) in patients with prostate cancer in combination with PSA expression, alkaline phosphatase and tumor differentiation on the Gleason scale as prognostic factors.
Materials and methods. Cross-sectional retrospective study was conducted on the basis of the clinic of the Regional Oncology center Semey (now the Center of nuclear medicine and Oncology Semey) from January 1, 2017 to December 31, 2017. The criterion for inclusion of patients in the study was PSA level in blood serum above 10 ng/ml. Statistical processing of the results of the study was carried out with the help of the program SPSS (Statistical Package for the Social Sciences), version 20.0 for Windows (license of Semey state medical University).
Pearson correlation coefficient (r) was the basis of correlation analysis, as an equivalent expression of the quantitative measure of force and direction of the relationship between the two studied features.
Results: A statistically significant positive correlation between the stage of prostate cancer and the level of Ki67 expression, between the degree of tumor differentiation and the level of Ki-67 was established. There was a positive statistically significant strong relationship between the level of Ki-67 expression and the presence of metastases in regional lymph nodes, as well as distant metastases, a positive correlation between the average strength of Ki-67 expression level and alkaline phosphatase level, as well as a strong positive correlation between the level of Ki-67 expression and PSA concentration.
A statistically significant strong positive relationship between the level of p53 expression and the presence of distant metastases (r=0.769; p=0.001), between the level of p53 expression and the size of the primary tumor (r=0.844; p=0.03) and between the level of p53 expression and the presence of metastases in regional lymph nodes (r=0.871; p=0.01) was proved.
Conclusions: The study proved the diagnostic and prognostic value of the study of the clinical expression of immunohistochemical markers (Ki67, P53) in patients with prostate cancer in combination with PSA expression, alkaline phosphatase and tumor differentiation on the Gleason scale as prognostic factors.
Erlan А. Ospanov 1, http://orcid.org/0000-0002-1344-5477
Тasbolat А. Аdylkhanov 1, http://orcid.org/0000-0002-9092-5060
1 «Semey Medical University» NJSC, Semey city, Republic of Kazakhstan
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8. Bauer J.J., Sesterhenn I.A., Mostofi F.K. et al. Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer. J Urol. 1996. Vol.156, № 4. P.1511-1516.
9. Berney D.M., Gopalan A., Kudahetti S., Fisher G., Ambroisine L., Foster C.S., Reuter V., Eastham J. et al. Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study // Br J Cancer. 2009.Vol.100, №6. P.888-893.
10. Borre M., Stausbol-Gron B., Nerstrom B., Overgaard J. Immunohistochemical BCL-2 and Ki-67 expression predict survival in prostate cancer patients followed expectantly. Prostate Cancer Prostatic Dis. 1998. Vol.1. P.268–275.
11. Bullwinkel J., Baron-Lühr B., Lüdemann A., Wohlenberg C., Gerdes J., Scholzen T. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. J. Cell. Physiol. 2006. Vol. 206, №3. P. 624–635.
12. Concato J., Jain D., Uchio E. et al. Molecular markers and death from prostate cancer. Ann Intern Med. 2009. Vol.150, №9. P.595-603.
13. Fonseca G.N., Srougi M., Leite K.R. et al. The role of HER2 / neu, BCL2, p53 genes and proliferating cell nuclear protein as molecular prognostic parameters in localized prostate carcinoma. Sao Paulo Med J. 2004. Vol. 122, №3. P.124-127.
14. Inoue T., Segawa T., Shiraishi T. et al. Androgen receptor, Ki67, and p53 expression in radical prostatectomy specimens predict treatment failure in Japanese population. Urol. 2005. Vol.66, № 32. P.2-7.
15. Khor L.Y., Bae K., Paulus R., Al-Saleem T., Elizabeth H. M., Grignon D.J., Che M., Venkatesan V. et al. MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer: RTOG 92-02. Am J Clin Oncol. 2009. Vol.27. P. 3177–3184.
16. Kluth M., Harasimowicz S, Burkhardt L, et al. Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer. Int J Cancer. 2014. Vol.135, №13. P.1369-13805
17. Kudahetti S., Fisher G., Ambroisine L., Foster C., Reuter V., Eastham J., Møller H., Kattan M.W. et al. p53 immunochemistry is an independent prognostic marker for outcome in conservatively treated prostate cancer. BJU Int. 2009. Vol.104. P.20–24.
18. Missaoui N., Abdelkarim S.B., Mokni M., Hmissa S. Prognostic Factors of Prostate Cancer in Tunisian Men: Immunohistochemical Study. Asian Pac J Cancer Prev. 2016. Vol.17, №5. P. 26-55.
19. Quinn D.I., Henshall S.M., Sutherland R.L. Molecular markers of prostate cancer outcome. Eur J Cancer. 2005. Vol. 41, №8. P. 58-87.
20. Ritter M.A., Gilchrist K.W., Voytovich M., Chappell R.J., Verhoven B.M. The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2002. Vol.53. P.574–580.
21. Rubio J., Ramos D., Lopez-Guerrero J.A., Iborra I., Collado A., et al. Immunohistochemical expression of ki-67 antigen, cox-2 and bax/bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens. Eur. Urol. 2005. Vol. 48, №5. P. 745-751.
22. Sonnenblick A., Francis P.A., Azim H.A., de Azambuja E., Nordenskjöld B., Gutiérez J., Quinaux E., Mastropasqua M.G., et al. Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer. European Journal of Cancer. 2015. Vol. 51, №12. P. 1481–1489.
23. Verhoven B., Yan Y., Ritter M. et al. Ki-67 is an independent predictor of metastasis and cause-specific mortality for prostate cancer patients treated on Radiation Therapy Oncology Group (RTOG). Int J Radiat Oncol Biol Phys. 2013. Vol.86, №3. P.17-23
24. Yerushalmi R., Woods R., Ravdin P.M., Hayes M.M., Gelmon K.A. Ki67 in breast cancer: prognostic and predictive potential. The Lancet. Oncology. 2010. Vol. 11, №2. P. 174–183.
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Ospanov E.А., Аdylkhanov Т.А. Prognostic significance of Ki-67, P53 in patients with prostate cancer and their correlation with standard indicators // Nauka i Zdravookhranenie [Science & Healthcare]. 2019, (Vol.21) 4, pp. 80-89.Related publications:
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