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Prostate Cancer Pathology

An emerging picture of prostate cancer development suggests that the silencing of gultathione S-transferase pi [GSTP1] makes the prostate cell more susceptible to DNA damage by carcinogens. A pathway of damage from prostatic inflammatory atrophy to prostatic intraepithelial neoplasia to frank prostate cancer has been put forth as a model of disease progression. Genetic deletion models in mice suggest that silencing or alterations in several other key molecules contribute to the development of cancer. These include NKX3.1, a gene responsible for prostate development. PTEN which acts in the PI3K signal transduction pathway and p27, a cyclin-dependent kinase inhibitor.

  • Proliferative inflammatory atrophy [PIA]. Focal areas of epithelial atrophy adjacent to PIN or carcinoma. These lesions demonstrate genetic alterations associated with prostate cancer and signs of cellular stress. A probable precursor of prostate cancer
  • Prostatic intraepithelial neoplasia [PIN]. Proliferation of acinar epithlium displaying varying grades of cytologic abnormalities. High grade PIN is associated with a 20-40 percent chance of demonstrating frank carcinoma on repeat biopsy. Progression from PIN to cancer may occur in 20-50 percent of cases.
  • Prostate carcinoma
    • Malignant
      • Conventional adenocarcinoma (small acinar carcinoma). The vast majority (95 to 97 percent) of prostate cancer is adenocarcinoma derived from acioar epithelium. The majority of lesions arise in the peripheral zone of the prostate gland. Approximately 20 to 25 percent of adenocarcinomas arise from the transitional zone. Classically, these tumors are discovered after TURP and described as stage la or lb disease. The grading and staging of this entity is discussed elsewhere. Histologic variants include the following.
      • Ductal or endometriod carcinoma. Displays exuberant papillary growth into prostatic ducts, which may be seen endoscopically. Usually present at advanced stages. May have a poor prognosis, stage for stage, than conventional adenocarcinoma.
      • Mucinous adenocarcinoma. More than 25 percent of the tumor must be composed of mucing containing glands to qualify for this diagnosis. Prognosis may be equal or worse than with conventional prostatic adenocarcinoma.
      • Signet cell carcinoma. Very poor prognosis. Most patients die with 40 months of diagnosis.
      • Small cell carcinoma. Neuroendocrine carcinoma of the prostate is rare and has been confused with poorly differentiated adenocarcinoma. The precursor cells, however, secrete different neuropeptides and may play a role in the hormonal refractory phenotype of prostate cancer. The diagnosis carries a very poor prognosis, although some patients show a partial response to radiotherapy and chemotherapy with VP-16 (etoposide) and cis-platinum.
  • Transitional Cell carcinoma (TCC) TCC of the prostate may be derived from major ducts of the prostate near the urethra. It is seen as the direct extension of a bladder tumor or as separate foci of cancer in the prostate. The worst prognosis is seen in patients with stromal invasion. Patients with isolated CIS of the prostatic urethra should undergo TURP and subsequent BCG intravesical therapy.
    • Sarcomas of the prostate are rare. In the adult population, leiomyosarcomas predominate. Prognosis is poor with an average 5-year survival rate of 40 percent. Rhabdomyosarcomas, which have a worse 5-year survival rate (0 to 10 percent), are generally seen in pediatric patients.
    • Metastatic tumors (colorectal, melanoma, lung, etc.)
    • Hematologic malignancies (lymphoma, plasmacytoma, leukemia involvement)
    • Patterns of spread.
      • Prostate tumors can spread by direct extension into the seminal vesicles and extracapsularly through the periprostatic nerve routes.
      • Direct extension into the rectum is uncommon. Ureteral obstruction can occur in 10 to 35 percent of patients during the course of their disease.
      • Lymphatic spread is not uncommon and occurs to the hypogastric, obturator, external iliac, presacral, common iliac, and paraaortic nodes in roughly that order.
      • Skip metastases are rare. Ninety percent of distant metastases are osseous. Visceral metastases to the lung, liver, and adrenals are less common and are rarely seen without bone involvement.

References

  • Albertson PC, Hanley JA, Gleason DR, Barry MJ: Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 280:975-980, 1998.
  • Cooney, K. A., J. D. McCarthy, et al. (1997). "Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study." J Natl Cancer Inst 89(13): 955-9.
  • Devgan, S. A., B. E. Henderson, et al. (1997). "Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk." Prostate 33(1): 9-12.
  • Greenlee, R. T., T. Murray, et al. (2000). "Cancer statistics, 2000." CA Cancer J Clin 50(1): 7-33.
  • Jemal, A., T. Murray, et al. (2003). "Cancer statistics, 2003." CA Cancer J Clin 53(1): 5-26.
  • Kalapurakal, J. A., A. N. Jacob, et al. (1999). "Racial differences in prostate cancer related to loss of heterozygosity on chromosome 8p12-23." Int J Radiat Oncol Biol Phys 45(4): 835-40.
  • Makridakis, N., R. K. Ross, et al. (1997). "A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase." Cancer Res 57(6): 1020-2.
  • Makridakis, N. M., R. K. Ross, et al. (1999). "Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA." Lancet 354(9183): 975-8.
  • Pettaway, C. A., P. Troncoso, et al. (1998). "Prostate specific antigen and pathological features of prostate cancer in black and white patients: a comparative study based on radical prostatectomy specimens." J Urol 160(2): 437-42.
  • Platz, E. A., M. N. Pollak, et al. (1999). "Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men." Cancer Epidemiol Biomarkers Prev 8(12): 1107-10.
  • Ross, R. K., L. Bernstein, et al. (1992). "5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males." Lancet 339(8798): 887-9.
  • Sakr, W. A., D. J. Grignon, et al. (1995). "Epidemiology of high grade prostatic intraepithelial neoplasia." Pathol Res Pract 191(9): 838-41.
  • Smith, J. R., D. Freije, et al. (1996). "Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search." Science 274(5291): 1371-4.
  • Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004 May 27;350(22):2239-46.
  • Tricoli, J. V., D. L. Winter, et al. (1999). "Racial differences in insulin-like growth factor binding protein-3 in men at increased risk of prostate cancer." Urology 54(1): 178-82.
  • Winter, D. L., A. L. Hanlon, et al. (2001). "Plasma levels of IGF-1, IGF-2, and IGFBP-3 in white and African-American men at increased risk of prostate cancer." Urology 58(4): 614-8.
  • Xu, J., D. Meyers, et al. (1998). "Evidence for a prostate cancer susceptibility locus on the X chromosome." Nat Genet 20(2): 175-9.