MOLECULAR PATHOGENESIS OF PROSTATE CANCER
Year 2022,
Volume: 29 Issue: 4, 697 - 706, 27.12.2022
Onur Ertunç
,
Burçin Tuna
Abstract
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.
References
- 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.
PROSTAT KANSERİ MOLEKÜLER PATOGENEZİ
Year 2022,
Volume: 29 Issue: 4, 697 - 706, 27.12.2022
Onur Ertunç
,
Burçin Tuna
Abstract
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.
References
- 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.