Molecular Biology of Prostate Cancer and Role of Genomic Testing in Diagnosis and Prognosis of Prostate Cancer

  • Rajal B. ShahEmail author
  • Ming Zhou


Prostate cancer, like other cancers, develops as the result of multiple, complex molecular events of initiation, unregulated growth, invasion, and metastasis. These complex molecular events include both loss of specific genomic sequences that lead to inactivation of tumor suppressor genes and gain of specific chromosome regions that are associated with activation of oncogenes. In prostate carcinogenesis, androgen receptor is believed to play a central role. The most common chromosomal aberrations demonstrated in prostatic carcinoma are TMPRSS2: ETS gene fusions, PTEN deletion, TP53 gene mutation, gain of chromosome 7 (particularly 7q31), loss of 8p and gain of 8q, and loss of 10q, 16q, and 18q.

Serum prostate-specific antigen (PSA) has remained the mainstay biomarker for the prostate cancer diagnosis and management since its widespread utilization as a screening tool almost 25 years ago. Although it has led to a dramatic increase in prostate cancer detection, PSA has substantial drawbacks both with sensitivity and specificity. Detection of clinically insignificant disease is another important issue. Together, these drawbacks of PSA emphasize the need for biomarkers that can supplement PSA as a diagnostic test, provide better cancer specificity than currently available tissue-based markers, reduce the number of unnecessary biopsies, and distinguish indolent from clinically significant prostate cancer. New genomic and bioinformatics technologies have discovered and enabled to study an expanding universe of novel tissue, urine, or body fluid-based biomarkers due to their higher cancer specificity or its prognostic or predictive utility. Such efforts have also produced several notable success stories that involve rapidly moving biomarkers from the bench to the clinic.

This chapter summarizes current understanding of molecular prostate carcinogenesis, types of PSA measurements utilized in clinical practice, and potential application of some of the most promising liquid biopsy and tissue-based biomarkers in the diagnosis and management of prostate cancer. For many of these proposed biomarkers, additional studies are needed to validate their clinical utility. In addition, it is important to keep in mind that biomarker development and validation is affected by many compounding pre-, intra-, and post-analytic factors.


Chromosomal aberrations Prostatic intraepithelial neoplasia (PIN) HGPIN Proliferative inflammatory atrophy (PIA) TMPRSS2: ETS gene fusions TMPRSS2: ERG gene fusions ERG PTEN deletion PTEN Prostate-specific antigen (PSA) PSA derivatives PSA isoforms Free PSA Total PSA proPSA Prostate health index (PHI) PCA3 T2-ERG GSTP1 α-Methylacyl-CoA racemase (AMACR) HPC1 GOLPH2 Sarcosine SPINK1 SPOP mutation Prostate-specific membrane antigen (PSMA) Prostate cell surface antigen (PCSA) EZH2 p27 ki67 Liquid biopsy ExoDx prostate 4KScore test Confirm MDx PINgenius Prostate Core Mitomic Test Oncotype Dx Prolaris Decipher Metamark 


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Robert J Tomsich Pathology and Laboratory Medicine InstituteCleveland ClinicClevelandUSA
  2. 2.Tufts Medical CenterBostonUSA

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