PATHOLOGY

What’s New in Prostate Cancer Disease Assessment in 2006?
Epstein JI
Departments of Disease, Urology, and Oncology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
Curr Opin Urol. 2006; 16: 146-51

• Purpose of Review: Issues relating to the disease are critical in the diagnosis, management, and prognostication of prostate cancer.
• Recent Findings: New data have emerged regarding the disease of prostate cancer and its precursors. The diagnosis of prostate cancer on needle biopsy has been refined because of the recent discovery of alpha-methylacyl-CoA racemase, which preferentially labels adenocarcinoma of the prostate. Modifications and additions to the Gleason grading system were published based on a consensus conference of urological pathologists. Various models have been proposed using Gleason score, clinical findings, as well as measurements of tumor volume on needle biopsy to enhance the prediction in men undergoing radical prostatectomy and to predict “insignificance”. Several studies have confirmed that certain findings in radical prostatectomy are adverse, yet conflicting studies were published as to the independent prognosis of tumor volume. The risk of cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy has decreased to the point at which this author does not recommend a routine repeat needle biopsy within the first year following the diagnosis of high-grade prostatic intraepithelial neoplasia.
• Summary: This review summarizes developments over the last year in the disease of prostate cancer and its precursors.
  
  
• Editorial Comment
  Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme first purified and characterized by investigators studying lipid metabolism. Although the role of this enzyme is still unknown, the application of AMACR immunohistochemistry in prostate pathology has been increased sharply in the last few years. AMACR preferentially labels adenocarcinoma of the prostate. In cases that the basal cells are patchy or discontinuous this labeling may be very useful for the differential diagnosis. Unfortunately, AMACR does not stain exclusively neoplastic acini. Benign acini may also show positivity, therefore, this stain should be used with caution (1).
  Due to the widespread use of extended needle prostatic biopsies, Epstein does not recommend a routine repeat needle biopsy within the first year following the diagnosis of high-grade prostatic intraepithelial neoplasia. This recommendation is based on studies showing a substantially decreasing in subsequent cancer detection if high-grade prostatic intraepithelial neoplasia is seen in extended biopsies (2).
  An important contribution for the improvement of the Gleason grading system was given by a Consensus Conference sponsored by the International Society of Urological Pathology (ISUP) during the USCAP (United States and Canadian Academy of Pathology) meeting in San Antonio, Texas, in 2005 (3).
  There are several arguments favoring a need for a consensus on Gleason grading: 1)- In the 1960s, there was no screening for prostate cancer other than by digital rectal examination, 2)- The use of 18-gauge thin biopsy needles and the concept of sextant needle biopsies to more extensively sample the prostate were not developed until the 1980s, 3)- Tertiary patterns were not addressed within the original Gleason system, 4)- The Gleason system predated the use of immunohistochemistry (it is likely that many of Gleason’s original 1 + 1 = 2 adenocarcinomas would today be regarded as adenosis, 5)- The original Gleason grading system was not applied to newly described variants of adenocarcinoma of the prostate; and, 6)- The Gleason system varies considerably in contemporary surgical pathology practice and has led to several recent attempts to achieve consensus on Gleason grading.
  A recent study in our Institution (4) showed that the highest impact of the consensus recommendations on a series of cases graded according to the standard Gleason system was seen on the secondary pattern, which had the lowest percentage of concordance. It reflected in a change toward a higher Gleason grading group in 46/172 (26.74%) of the cases. A further study showed that these 46 patients had significantly a higher preoperative PSA, had more extensive tumors in the surgical specimen, had higher frequency of positive surgical margins and pathologic stage, and a strong tendency for shorter time to biochemical (PSA) progression-free survival following radical prostatectomy. The recommendations of the ISUP are a valuable refinement for the standard Gleason grading system and should be used by pathologists in their routine practice.

References
1. Jiang Z, Fanger GR, Woda BA, Banner BF, Algate P, Dresser K, et al.: Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: a study of 761 cases. Hum Pathol. 2003; 34: 792-6.
2. Herawi M, Kahane H, Cavallo C, Epstein JI: Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of high grade prostatic intraepithelial neoplasia is related to the number of cores sampled. J Urol. 2006; 175: 121-4.
3. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005; 29: 1228-42.
4. Guimaraes MS, Billis A, Quintal MM, Magna LA, Ferreira U: The impact of the 2005 International Society of Urological Pathology (ISUP) Consensus Conference on standard Gleason grading of prostatic carcinoma. Mod Pathol Suppl. 2006; 1: 139A.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, Sao Paulo, Brazil