Prostate cancer pathophysiology

Jump to navigation Jump to search

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Syed Musadiq Ali M.B.B.S.[2]

Prostate cancer Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Prostate Cancer from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Staging

Laboratory Findings

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Biopsy

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Alternative Therapy

Case Studies

Case #1

Prostate cancer pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Prostate cancer pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Prostate cancer pathophysiology

CDC on Prostate cancer pathophysiology

Prostate cancer pathophysiology in the news

Blogs on Prostate cancer pathophysiology

Directions to Hospitals Treating Prostate cancer

Risk calculators and risk factors for Prostate cancer pathophysiology

Overview

On microscopic histopathological analysis, increased gland density, small circular glands, basal cells lacking, and cytological abnormalities are characteristic findings of prostate cancer.

Pathogenesis

  • Prostate cancers can be lethal because they heterogeneously contain both androgen-dependent and androgen-independent malignant cells[1]
  • For those cells that are androgen dependent, a critical level of androgen is required to activate a sufficient number of androgen receptors (ARs) so that transcription of death-signaling gene is expressed
  • Androgens are capable of both stimulating proliferation as well as inhibiting the rate of the glandular epithelial cell death
  • Androgen withdrawal triggers the programmed cell death pathway in both normal prostate glandular epithelia and androgen-dependent prostate cancer cells
  • Androgen-independent prostate cancer cells do not initiate the programmed cell death pathway upon androgen ablation; however, they do retain the cellular machinery necessary to activate the programmed cell death cascade when sufficiently damaged by exogenous agents

Inherited Prostate-Cancer–Susceptibility Genes

  • Rare autosomal dominant alleles account for a substantial proportion of cases of inherited, early-onset prostate cancer (defined as cancer occurring before 55 years of age)[2]
  • In families with men in whom prostate cancer is diagnosed at an older age, an X-linked allele may be responsible [3]
  • The first molecular genetic study of familial prostate cancer in which polymorphic markers were used identified several regions of linkage; the chromosomal region 1q24–25, designated the locus of the hereditary prostate cancer (HPC1) gene, has been the most thoroughly investigated[4]
  • Some analyses have confirmed a link between HPC1 and prostate cancer, but others have failed to detect an association[5]

RNASEL

MSR1

AR, CYP17, AND SRD5A2

  • Although there is no proof that PIN is a cancer precursor, it is closely associated with cancer. Over time these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.[18]
When normal cells are damaged beyond repair, they are eliminated by apoptosis. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.


Gross Pathology

Prostate cancer is uncommonly apparent on gross.[20]

Microscopic Pathology

Major criteria:[21][22]

  • Architecture
  • Increased gland density
  • Small circular glands
  • In rare subtypes - large branching glands
  • Basal cells lacking
  • Cytological abnormalities:

Minor criteria:

Prostate adenocarcinoma: Microscopic View

{{#ev:youtube|1SZPLS1dxTo}}

Gleason score

Prostate: Adenocarcinoma (Gleason grade 1)

{{#ev:youtube|F7V0Zl7a2FY}}

Prostate: Adenocarcinoma (Gleason grade 2)

{{#ev:youtube|YSOLiSklIXw}}

Prostate: Adenocarcinoma (Gleason grade 3)

{{#ev:youtube|TG8vR_pE7yA}}

Prostate: Adenocarcinoma (Gleason grade 4)

{{#ev:youtube|R2Cl4HScdGc}}

Prostate: Adenocarcinoma (Gleason grade 5)

{{#ev:youtube|F7V0Zl7a2FY}}

References

  1. Denmeade SR, Lin XS, Isaacs JT (April 1996). "Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer". Prostate. 28 (4): 251–65. doi:10.1002/(SICI)1097-0045(199604)28:4<251::AID-PROS6>3.0.CO;2-G. PMID 8602401.
  2. Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC (April 1992). "Mendelian inheritance of familial prostate cancer". Proc. Natl. Acad. Sci. U.S.A. 89 (8): 3367–71. PMC 48868. PMID 1565627.
  3. Cui J, Staples MP, Hopper JL, English DR, McCredie MR, Giles GG (May 2001). "Segregation analyses of 1,476 population-based Australian families affected by prostate cancer". Am. J. Hum. Genet. 68 (5): 1207–18. doi:10.1086/320114. PMC 1226101. PMID 11309686.
  4. Smith JR, Freije D, Carpten JD, Grönberg H, Xu J, Isaacs SD, Brownstein MJ, Bova GS, Guo H, Bujnovszky P, Nusskern DR, Damber JE, Bergh A, Emanuelsson M, Kallioniemi OP, Walker-Daniels J, Bailey-Wilson JE, Beaty TH, Meyers DA, Walsh PC, Collins FS, Trent JM, Isaacs WB (November 1996). "Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search". Science. 274 (5291): 1371–4. PMID 8910276.
  5. Ostrander EA, Stanford JL (December 2000). "Genetics of prostate cancer: too many loci, too few genes". Am. J. Hum. Genet. 67 (6): 1367–75. doi:10.1086/316916. PMC 1287913. PMID 11067781.
  6. Silverman RH, Jung DD, Nolan-Sorden NL, Dieffenbach CW, Kedar VP, SenGupta DN (May 1988). "Purification and analysis of murine 2-5A-dependent RNase". J. Biol. Chem. 263 (15): 7336–41. PMID 3366783.
  7. Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, Faruque M, Moses T, Ewing C, Gillanders E, Hu P, Bujnovszky P, Makalowska I, Baffoe-Bonnie A, Faith D, Smith J, Stephan D, Wiley K, Brownstein M, Gildea D, Kelly B, Jenkins R, Hostetter G, Matikainen M, Schleutker J, Klinger K, Connors T, Xiang Y, Wang Z, De Marzo A, Papadopoulos N, Kallioniemi OP, Burk R, Meyers D, Grönberg H, Meltzer P, Silverman R, Bailey-Wilson J, Walsh P, Isaacs W, Trent J (February 2002). "Germline mutations in the ribonuclease L gene in families showing linkage with HPC1". Nat. Genet. 30 (2): 181–4. doi:10.1038/ng823. PMID 11799394.
  8. Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Hu JJ, Sterling D, Lange EM, Hawkins GA, Turner A, Ewing CM, Faith DA, Johnson JR, Suzuki H, Bujnovszky P, Wiley KE, DeMarzo AM, Bova GS, Chang B, Hall MC, McCullough DL, Partin AW, Kassabian VS, Carpten JD, Bailey-Wilson JE, Trent JM, Ohar J, Bleecker ER, Walsh PC, Isaacs WB, Meyers DA (October 2002). "Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk". Nat. Genet. 32 (2): 321–5. doi:10.1038/ng994. PMID 12244320.
  9. Platt N, Gordon S (September 2001). "Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse's tale". J. Clin. Invest. 108 (5): 649–54. doi:10.1172/JCI13903. PMC 209390. PMID 11544267.
  10. Dejager S, Mietus-Snyder M, Friera A, Pitas RE (August 1993). "Dominant negative mutations of the scavenger receptor. Native receptor inactivation by expression of truncated variants". J. Clin. Invest. 92 (2): 894–902. doi:10.1172/JCI116664. PMC 294928. PMID 8349824.
  11. Edwards A, Hammond HA, Jin L, Caskey CT, Chakraborty R (February 1992). "Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups". Genomics. 12 (2): 241–53. PMID 1740333.
  12. Chamberlain NL, Driver ED, Miesfeld RL (August 1994). "The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function". Nucleic Acids Res. 22 (15): 3181–6. PMC 310294. PMID 8065934.
  13. Bennett CL, Price DK, Kim S, Liu D, Jovanovic BD, Nathan D, Johnson ME, Montgomery JS, Cude K, Brockbank JC, Sartor O, Figg WD (September 2002). "Racial variation in CAG repeat lengths within the androgen receptor gene among prostate cancer patients of lower socioeconomic status". J. Clin. Oncol. 20 (17): 3599–604. doi:10.1200/JCO.2002.11.085. PMID 12202660.
  14. Irvine RA, Yu MC, Ross RK, Coetzee GA (May 1995). "The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer". Cancer Res. 55 (9): 1937–40. PMID 7728763.
  15. Haiman CA, Stampfer MJ, Giovannucci E, Ma J, Decalo NE, Kantoff PW, Hunter DJ (July 2001). "The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer". Cancer Epidemiol. Biomarkers Prev. 10 (7): 743–8. PMID 11440959.
  16. 16.0 16.1 Nam RK, Toi A, Vesprini D, Ho M, Chu W, Harvie S, Sweet J, Trachtenberg J, Jewett MA, Narod SA (January 2001). "V89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression". Urology. 57 (1): 199–204. PMID 11164181.
  17. "Prostate Cancer". National Cancer Institute. Retrieved 12 October 2014.
  18. 18.0 18.1 18.2 18.3 "Male Genitals - Prostate Neoplasms". Pathology study images. University of Virginia School of Medicine. Archived from the original on 2011-04-28. Retrieved 2011-04-28. There are many connections between the prostatic venous plexus and the vertebral veins. The veins forming the prostatic plexus do not contain valves and it is thought that straining to urinate causes prostatic venous blood to flow in a reverse direction and enter the vertebral veins carrying malignant cells to the vertebral column.
  19. . doi:10.9790/0853-1506020411. Missing or empty |title= (help)
  20. Prostatic carcinoma.Dr Ian Bickle and Dr Saqba Farooq et al. Radiopaedia.org 2015.http://radiopaedia.org/articles/prostatic-carcinoma-1
  21. Humphrey PA (2007). "Diagnosis of adenocarcinoma in prostate needle biopsy tissue". J. Clin. Pathol. 60 (1): 35–42. doi:10.1136/jcp.2005.036442. PMC 1860598. PMID 17213347. Unknown parameter |month= ignored (help)
  22. "Prostate cancer.Libre pathology 2015".

Template:WH Template:WS