Does high grade prostatic intraepithelial neoplasia result in elevated serum prostate specific antigen levels?

Prior studies have evaluated high grade prostatic intraepithelial neoplasia on biopsy material when undiagnosed carcinoma or benign prostatic hyperplasia (BPH) may have been associated with elevated serum prostate specific antigen (PSA) levels. We studied 65 totally embedded radical prostatectomy specimens with minimal carcinoma (tumor volume 0.5 cc or less) and relatively minimal BPH (gland weight less than 65 gm.). Even for these relatively small glands, PSA showed a significant correlation with gland volume (r = 0.64). To account for BPH, PSA density (PSA divided by gland volume) was also calculated. In these specimens with trivial tumor the tumor volume did not correlate with PSA (r = 0.12) or PSA density (r = 0.23). The volume of high grade prostatic intraepithelial neoplasia also showed no correlation with PSA (r = 0.16) or PSA density (r = 0.14). The 11 cases with extensive high grade prostatic intraepithelial neoplasia (0.50 cc or more) had PSA density values of 0.03 to 0.14, with 10 less than 0.1. Of the 6 cases with PSA density values of 0.1 or more only 1 had a high grade prostatic intraepithelial neoplasia volume of 0.5 cc or more. These results indicate that high grade prostatic intraepithelial neoplasia in and of itself does not account for elevated serum PSA levels. In a patient with high grade prostatic intraepithelial neoplasia on biopsy material and elevated serum PSA values, BPH may account for the elevated serum PSA levels. More likely, because of the association between high grade prostatic intraepithelial neoplasia and carcinoma these patients have undiagnosed carcinoma as the source of the elevated serum PSA values.