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PROSTAT KANSERİ MOLEKÜLER PATOGENEZİ

Prostat kanseri dünya genelinde erkeklerde akciğer karsinomundan sonra 2. en sık ölüme yol açan kanserlerdir. Her ne kadar erken tedavi ve koruyucu hekimlik uygulamalarının PSA takibi şeklinde ön plana çıkmasıyla, devamında iğne biyopsilerle hastaların tümör gelişiminin saptanması kolaylaşmış olsa da tümörün özellikle tedavi öncesinde, sırasında ve sonrasındaki davranışlarının belirlenmesi anlamında elimizde risk skorlama şemaları dışında pek bir şansımız yoktu. Günümüzde kişiye özgü tedavi modellerini belirlemede ve hastalığın ileri evre olmadan prognozunu tahmin etmede kullanabileceğimiz moleküler imzası ve moleküler biyolojisi önem arz etmektedir. Tüm bu nedenlerle prostat kanserinin moleküler patogenezi ve biyolojik davranışının medikal profesyoneller tarafından bilinmesi hastalığı ve seyrini anlamada bize yardımcı olacaktır.

Anahtar Kelimeler:

ETS pozitif ve negatif PCa, İleri evre hastalık, Moleküler patogenez, Prostat biyolojisi, Prostat kanseri

MOLECULAR PATHOGENESIS OF PROSTATE CANCER

Prostate cancer is the second most common cause of death in men worldwide, after lung carcinoma. Although early treatment and preventive medicine practices came to the fore in the era of PSA followup, and subsequent needle biopsies made it easier to detect the tumor development of the patients, but we did not have much chance in terms of determining the behavior of the tumor especially before, during and after the treatment, except for risk scoring schemes. Today, the molecular signature and molecular biology of the disease, which we can use to determine individual treatment models and to predict the prognosis of the disease, are important. For all these reasons, medical professional's knowledge of the molecular pathogenesis and biological attitude of prostate cancer will help to understand the disease and its course.

Keywords:

Advanced disease, Biology of prostate, ETS positive and negative PCa, Molecular pathogenesis, Prostate cancer ETS pozitif ve negatif PCa, İleri evre hastalık, Moleküler patogenez, Prostat biyolojisi, Prostat kanseri,

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1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72: 7–33.
2. Zorlu F, Zorlu R, Divrik RT, Eser S, Yorukoglu K. Prostate cancer incidence in Turkey: an epidemiological study. Asian Pac J Cancer Prev. 2014;15: 9125–9130.
3. Hoffman RM. Screening for prostate cancer [Internet]. Up- ToDate Waltham, MA 2021 [cited 2022 Dec 25]. Available from: https://www.uptodate.com/contents/screening-for-prostate- cancer?search=Screening%20for%20prostate%20cancer&- source=search_result&selectedTitle=1~150&usage_type=default& display_rank=1
4. Oliver SA. Risk factors for prostate cancer [Internet]. UpToDate Waltham, MA 2022 [cited 2022 Dec 25]. Available from: https:// www.uptodate.com/contents/risk-factors-for-prostate-cancer?- search=Risk%20factors%20for%20prostate%20cancer.&source= search_result&selectedTitle=1~150&usage_type=default& display_rank=1
5. Etzioni R, Gulati R, Tsodikov A, Wever EM, Penson DF, Heijnsdijk EAM, et al. The prostate cancer conundrum revisited. Cancer. 2012;23: 5955–63.
6. Klein EA. Localized prostate cancer: Risk stratification and choice of initial treatment [Internet]. UpToDate Waltham, MA 2022. [cited 2022 Dec 25]. Available from: https://www.uptodate.com/ contents/localized-prostate-cancer-risk-stratification-and-choice- of-initial-treatment?search=Klein%20EA.%20Localized%20 prostate%20cancer:%20Risk%20stratification%20and%20 cho%20ice%20of%20initial%20treatment.%20&source=search_ result&selectedTitle=1~150&usage_type=default&display_ rank=1
7. Powell IJ. Epidemiology and pathophysiology of prostate cancer in African-American men. J Urol. 2007;177: 444–449.
8. Stanford JL, Ostrander EA. Familial prostate cancer. Epidemiol Rev. 2001;23: 19–23.
9. Grummet J, Eggener S. Re: NCCN Prostate Cancer Guidelines Version 1.2022 – September 10, 2021. European Urology. 2022. p. 218.
10. Testa U, Castelli G, Pelosi E. Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications. Medicines. 2019;6(3):82
11. McNeal JE. Origin and development of carcinoma in the prostate. Cancer. 1969;23: 24–34.
12. Jr D. Introductory remarks and workshop summary. Urology. 1989;34: 2–3.
13. Varma M, Delahunt B, Egevad L, Samaratunga H, Kristiansen G. Intraductal carcinoma of the prostate: a critical re-appraisal. Virchows Arch. 2019;474: 525–534.
14. Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs—part B: Prostate and bladder tumours. Eur Urol. 2016;70: 106–119.
15. Chrisofos M, Papatsoris AG, Lazaris A, Deliveliotis C. Precursor lesions of prostate cancer. Crit Rev Clin Lab Sci. 2007;44(3):243–70.
16. Nelson WG, Antonarakis ES, Carter HB, De Marzo AM, DeWeese TL. Prostate Cancer. In: Niederhuber JE, Armitage JO, Kastan MB, Doroshow JH, Tepper JE. Abeloff’s Clinical Oncology (Sixth Edition). Philadelphia: Elsevier; 2020; 1401–1432.
17. Erzurumlu Y. Prostat Kanseri: Androjen Reseptörü Sinyal Mekanizması. SDÜ Tıp Fakültesi Dergisi. 2021;28(1):187–98.
18. Andrew J. Stephenson, Klein EA. Epidemiology, Etiology, and Prevention of Prostate Cancer. In: Alan WP, Roger RD, Louis RK, Craig AP. Campbell Walsh Wein Urology (Twelfth Edition). Philadelphia: Elsevier; 2021; 3457–3477.
19. Arora K, Barbieri CE. Molecular Subtypes of Prostate Cancer. Curr Oncol Rep. 2018;20: 58.
20. Yuan T-C, Veeramani S, Lin F-F, Kondrikou D, Zelivianski S, Igawa T, et al. Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. Endocr Relat Cancer. 2006;13: 151–167.
21. Kuroda N, Katto K, Tamura M, Shiotsu T, Nakamura S, Ohtsuki Y, et al. Immunohistochemical application of D2-40 as basal cell marker in evaluating atypical small acinar proliferation of initial routine prostatic needle biopsy materials. Med Mol Morphol. 2010;43: 165–169.
22. Netto GJ, Cheng L. Emerging critical role of molecular testing in diagnostic genitourinary pathology. Arch Pathol Lab Med. 2012;136: 372–390.
23. Griend DV. Molecular biology of prostate cancer [Internet]. Up- ToDate Waltham, MA 2021 [cited 2022 Dec 25] Available from: https://www.uptodate.com/contents/molecular-biology-of-prostate- cancer?source=mostViewed_widget
24. Sfanos KS, Gonzalgo ML. Molecular Genetics and Cancer Biology. In: Alan WP, Roger RD, Louis RK, Craig AP. Campbell Walsh Wein Urology (Twelfth Edition). Philadelphia: Elsevier; 2021; 1346–1369.
25. Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R, et al. Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell. 2003;4: 223–238.
26. Gurel B, Iwata T, Koh CM, Jenkins RB, Lan F, Van Dang C, et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol. 2008;21: 1156–1167.
27. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar- Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419: 624–629.
28. Varambally S, Yu J, Laxman B, Rhodes DR, Mehra R, Tomlins SA, et al. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell. 2005;8: 393–406.
29. Coleman WB. Molecular Pathogenesis of Prostate Cancer. In: Coleman WB, Tsongalis GJ. Molecular Pathology (Second Edition). Academic Press; 2018; 555–568.
30. Ratnacaram CK, Teletin M, Jiang M, Meng X, Chambon P, Metzger D. Temporally controlled ablation of PTEN in adult mouse prostate epithelium generates a model of invasive prostatic adenocarcinoma. Proc Natl Acad Sci U S A. 2008;105: 2521–2526.
31. Gumuskaya B, Gurel B, Fedor H, Tan H-L, Weier CA, Hicks JL, et al. Assessing the order of critical alterations in prostate cancer development and progression by IHC: further evidence that PTEN loss occurs subsequent to ERG gene fusion. Prostate Cancer Prostatic Dis. 2013;16: 209–215.
32. Krohn A, Freudenthaler F, Harasimowicz S, Kluth M, Fuchs S, Burkhardt L, et al. Heterogeneity and chronology of PTEN deletion and ERG fusion in prostate cancer. Mod Pathol. 2014;27: 1612–1620.
33. Mellado B, Codony J, Ribal MJ, Visa L, Gascón P. Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway. Clin Transl Oncol. 2009;11: 5–10.
34. Udager AM, Smith SC, Tomlins SA. Molecular Pathology of Prostate Cancer. In: Coleman WB, Tsongalis GJ. Diagnostic Molecular Pathology. Academic Press; 2016; 271–286.
35. Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010;18: 11–22.
36. Grasso CS, Wu Y-M, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, et al. The mutational landscape of lethal castration- resistant prostate cancer. Nature. 2012;487: 239–243.
37. Li L-C, Hsieh AC, Ruggero D, Greene KL, Carroll PR. Molecular Basis of Prostate Cancer. In: Mendelsohn J, Gray JW, Howley PM, Israel MA, Thompson CB. The Molecular Basis of Cancer (Fourth Edition). Philadelphia: W.B. Saunders; 2015; 549–560.
38. Sokolova AO, Cheng HH. Genetic Testing in Prostate Cancer. Curr Oncol Rep. 2020;22: 5.
39. Vlajnic T, Bubendorf L. Molecular pathology of prostate cancer: a practical approach. Pathology. 2021;53: 36–43.
40. Konaç E, Sözen S. Molecular biology in diagnosis and treatment of prostate cancer. Üroonkoloji bül. 2014;13: 228–235.
41. Barbieri CE, Bangma CH, Bjartell A, Catto JWF, Culig Z, Grönberg H, et al. The mutational landscape of prostate cancer. Eur Urol. 2013;64: 567–576.
42. Warrick JI, Tomlins SA. Prostate Cancer Molecular Prognosis. In: Robinson BD, Mosquera JM, Ro JY, Divatia M. Precision Molecular Pathology of Prostate Cancer. Cham: Springer; 2018; 503–522.
43. Quinn DI, Henshall SM, Sutherland RL. Molecular markers of prostate cancer outcome. Eur J Cancer. 2005;41: 858–887.
44. Faisal FA, Sundi D, Tosoian JJ, Choeurng V, Alshalalfa M, Ross AE, et al. Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location. Eur Urol. 2016;70: 14–17.
45. Cancer Genome Atlas Research Network. The Molecular Taxonomy of Primary Prostate Cancer. Cell. 2015;163: 1011–1025.
46. Cucchiara V, Cooperberg MR, Dall’Era M, Lin DW, Montorsi F, Schalken JA, et al. Genomic Markers in Prostate Cancer Decision Making. Eur Urol. 2018;73: 572–582.