PATHOLOGY

Serum PSA level correlates with the needle biopsy extent of atrophy and chronic inflammation, but not with high grade PIN and prostate cancer
Magi-Galluzzi C, Schoenfield L, Klein E, Jones S, Zhou M
Cleveland Clinic Foundation, Cleveland, OH, USA
Mod Pathol. 2005; 18 (suppl. 1): 154A

• Background: Serum prostate specific antigen (PSA) is the most common marker used to follow men with and without prostate cancer (PCa) and is used as a guide to initiate prostate biopsies. Recently, the value of serum PSA level in predicting the presence or absence of PCa has been questioned.
• Design: One hundred consecutive first time saturation prostate biopsies (PBx) performed by a single urologist between February 2003 and May 2004 and reviewed by two pathologists were included in the study. Biopsy criteria were defined as serum total PSA of 2.5 ng/mL or greater and/or abnormal findings on digital rectal examination. All patients underwent a 24-core biopsy protocol. Patient age, PSA, extent (% of tissue involved) of high grade prostatic intraepithelial neoplasia (PIN), % cancer, % atrophy, % chronic inflammation, and presence of acute inflammation were recorded.
• Results: The patients were divided in 3 groups: group A (n = 34 with atrophy only), group B (n = 29 with PIN and/or atypical glands), group C (n = 37 with PCa). Atrophy was detected in all cases, ranging from 1.4 to 62.2% of the tissue (mean 22.5%). Chronic inflammation (CI) was present in 98% of the cases, ranging from 0.2 to 44.6% of the tissue (mean 4.5%). Acute inflammation was present in 61% of the cases. The mean PSA and age of the patients for each group were: 7.4 ng/mL and 60.8 years (A); 5.2 ng/mL and 61.7 years (B); 6.0 ng/mL and 65.4 years (C). The difference in mean age between group A (atrophy) and C (PCa) was statistically significant (p = 0.045). No correlation was found between PSA and presence or extent of PIN and/or PCa either in the general population (A + B + C) or in the PCa and PIN group (B + C). The presence of PIN was associated with concurrent prostate cancer (p = 0.003). Serum PSA level in the general population correlated with the extent of atrophy (p = 0.022) and CI (p = 0.009).
• Conclusions: In this group of patients, preoperative serum PSA level does not correlate with the presence or absence, and extent of PCa and PIN. Atrophy and chronic inflammation are strong contenders for the PSA released into the serum at an increased level. PSA is a marker useful to follow up men with cancer, although its value as screening and staging tool is questionable.
  
  
• Editorial Comment
  The hypothesis that atrophy is a strong contender for the PSA release into the serum is challenging. We have just finished a paper dealing with this subject.
  There is evidence that age associated prostatic atrophy may be a manifestation of chronic ischemia due to local arteriosclerosis (1-4). In autopsies, there is a positive and statistically significant association between intense local arteriosclerosis and presence and extent of atrophy (1). The aim of our study was to find any association between extent of atrophy in prostate needle biopsies and serum prostate-specific antigen (PSA) levels (total, free or free/total ratio).
  The study was based on 136 needle prostatic biopsies corresponding to 123 patients. The only diagnosis in all biopsies was focal prostatic atrophy without presence of cancer, high-grade prostatic intraepithelial neoplasia (HGPIN), suspicious for cancer, or prostatitis. The data were analyzed subdividing the patients into 2 groups: with free/total serum PSA ³ 0.15 (Group 1, 61 biopsies), and with free/total PSA < 0.15 (Group 2, 75 biopsies). The extent of atrophy was evaluated considering either the absolute number or the percentage of cores showing the lesion. Polynomial regression or simple correlation were applied using in each analysis the most suitable function that best fitted to the distribution of the data.
  Group 1: there was a positive and statistically significant correlation between extent of atrophy and either free (p = 0.0076 and p = 0.0210, respectively, for parabolic and linear functions) or free/total PSA (p = 0.0068 and p = 0.0085, respectively, for 4th degree and parabolic functions); no correlation was found for total PSA. Group 2: no significant correlation was found between extent of atrophy and free, total or free/total PSA.
  Considering that age associated prostatic atrophy may be a manifestation of chronic ischemia due to local arteriosclerosis, the results suggest that chronic ischemia may be involved in free PSA serum level elevation in patients with several needle biopsies showing only prostatic atrophy and free/total PSA ³ 0.15.

References
1. Billis A: Prostatic atrophy: an autopsy study of a histologic mimic of adenocarcinoma, Mod Pathol. 1998; 11: 47-54.
2. Young RH, Srigley JR, Amin MB, Ulbright TM, Cubilla AL: Tumors of the Prostate Gland, Seminal Vesicles, Male Urethra, and Penis, Atlas of Tumor Pathology, Armed Forces Institute of Pathology, 3rd Series, fascicle 28, Washington DC, 2000.
3. Humphrey PA: Prostate Pathology. Chicago, ASCP Press. 2003.
4. Srigley JR: Benign mimickers of prostate cancer. Mod Pathol. 2004; 17: 328-48.

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