Abstract
Prostatic adenocarcinoma is the most common noncutaneous malignancy in men and the second leading cause of cancer death in Western populations. Despite its prevalence, an understanding of the molecular alterations affecting the development, progression, and treatment of the disease was largely lacking until recently. Rapid advances in molecular techniques in the past decade have seen a dramatic increase in our understanding of the role molecular alterations play in prostate cancer. Though still early, these developments have provided insight into distinct subsets of prostate cancer that promise to change how the disease is both diagnosed and managed. The molecular alterations discovered have shown that prostate cancer development involves multiple genetic abnormalities and that detection or targeting of a single genetic event is unlikely to impact all cases of prostate cancer. Of the ones that have shown the most promise to changing diagnostic and treatment paradigms are the gene fusion of TMPRSS2 and members of the ETS family of transcription factors, primarily ERG, as well as the inactivation of the tumor suppressor PTEN. A greater understanding of the molecular alterations present in prostate cancer will lead to further improvements in diagnosis, prediction of prognosis, stratification for specific therapies, and ultimately better outcomes for patients.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSuggested Reading
Andreoiu M, Cheng L. Multifocal prostate cancer: biologic, prognostic, and therapeutic implications. Hum Pathol. 2010;41(6):781–93.
Barbieri CE, Demichelis F, Rubin MA. Molecular genetics of prostate cancer: emerging appreciation of genetic complexity. Histopathology. 2012;60(1): 187–98.
Berger MF, Lawrence MS, Demichelis F, Drier Y, Cibulskis K, Sivachenko AY, et al. The genomic complexity of primary human prostate cancer. Nature. 2011;470:214–20.
Cheville JC, Karnes RJ, Therneau TM, et al. Gene panel model predictive of outcome in men at high-risk of systemic progression and death from prostate cancer after radical retropubic prostatectomy. J Clin Oncol. 2008;26(24):3930–6.
DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. Pathological and molecular aspects of prostate cancer. Lancet. 2003;361(9361):955–64.
Gurel B, Iwata T, Koh CM, Yegnasubramanian S, Nelson WG, De Marzo AM. Molecular alterations in prostate cancer as diagnostic, prognostic, and therapeutic targets. Adv Anat Pathol. 2008;15(6):319–31.
Karnes RJ, Cheville JC, Ida CM, et al. The ability of biomarkers to predict systemic progression in men with high-risk prostate cancer treated surgically is dependent on ERG status. Cancer Res. 2010;70(22): 8994–9002.
Kristiansen G. Diagnostic and prognostic molecular biomarkers for prostate cancer. Histopathology. 2012; 60(1):125–41.
Lotan TL, Toubaji A, Albadine R, et al. TMPRSS2–ERG gene fusions are infrequent in prostatic ductal adenocarcinomas. Mod Pathol. 2009;22(3):359–65.
Markert EK, Mizuno H, Vazquez A, Levine AJ. Molecular classification of prostate cancer using curated expression signatures. Proc Natl Acad Sci USA. 2011; 108(52):21276–81.
Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med. 2003;349(4):366–81.
Nelson WG, DeWeese TL, DeMarzo AM. The diet, prostate inflammation, and the development of prostate cancer. Cancer Metastasis Rev. 2002;21(1):3–16.
Perner S, Mosquera JM, Demichelis F, et al. TMPRSS2–ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. 2007; 31(6):882–8.
Perner S, Svensson MA, Hossain RR, et al. ERG rearrangement metastasis patterns in locally advanced prostate cancer. Urology. 2010;75(4):762–7.
Sfanos KS, De Marzo AM. Prostate cancer and inflammation: the evidence. Histopathology. 2012; 60(1):199–215.
Sreenath TL, Dobi A, Petrovics G, Srivastava S. Oncogenic activation of ERG: a predominant mechanism in prostate cancer. J Carcinog. 2011;10:37.
Tomlins SA, Bjartell A, Chinnaiyan AM, et al. ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol. 2009;56(2):275–86.
Tomlins SA, Laxman B, Dhanasekaran SM, et al. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature. 2007;448(7153):595–9.
Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644–8.
True L, Coleman I, Hawley S, et al. A molecular correlate to the Gleason grading system for prostate adenocarcinoma. Proc Natl Acad Sci USA. 2006;103(29): 10991–6.
Vogan K. HOXB13 and prostate cancer. Nat Genet. 2012;44:241.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Gurel, B., Alexander, R.E., Cheng, L., De Marzo, A.M. (2013). Molecular Pathology of Prostate Cancer. In: Cheng, L., Eble, J. (eds) Molecular Surgical Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4900-3_10
Download citation
DOI: https://doi.org/10.1007/978-1-4614-4900-3_10
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-4899-0
Online ISBN: 978-1-4614-4900-3
eBook Packages: MedicineMedicine (R0)