Precursor of prostate-specific antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 90 cases.

Objective: To assess the expression of the precursor of prostate-specific antigen (pro-PSA), a distinct molecular form of serum-free PSA that includes native and truncated forms, in benign epithelium, high-grade prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma.

Materials And Methods: We immunohistochemically evaluated 90 formalin-fixed, paraffin-embedded prostate needle biopsies using monoclonal antibodies against [-2] pro-PSA, native [-5/-7] pro-PSA, prostate-specific membrane antigen (PSMA), PSA and racemase. Staining intensity was recorded using a scale of 0-3 (0, no staining; 3, highest staining). The percentage of immunoreactive cells in benign epithelium, high-grade PIN and adenocarcinoma was estimated in increments of 10%.

Results: All cases had [-5/-7] pro-PSA immunoreactivity. There was weak focal perinuclear cytoplasmic immunoreactivity for [-5/-7] pro-PSA in 62% (range 0-90%) of benign epithelial cells, whereas there was strong diffuse cytoplasmic staining in 83% (range 10-90%) of high-grade PIN and 87% (range 40-90%) of cancer cells. Almost all (99%) cases were immunoreactive for [-2] pro-PSA. The median (range) proportion of cells expressing [-2] pro-PSA was lower in benign epithelium, at 17 (0-80)%, than in high-grade PIN, at 55 (0-90)% (P < 0.001) and adenocarcinoma, at 55 (0-100)% (P < 0.001). The intensity of immunoreactivity for both isoforms increased from benign to neoplastic (high-grade PIN and adenocarcinoma) epithelium. A total of 31% of high-grade PIN and 11% of cancer cases with negative racemase staining showed strong staining for [-5/-7] pro-PSA.

Conclusion: The expression of [-5/-7] pro-PSA in benign and neoplastic cells might be used in combination with high molecular weight keratin, p63, and racemase to distinguish benign epithelium from high-grade PIN and adenocarcinoma, particularly when racemase staining is negative. Both isoforms are sensitive markers for prostatic epithelium, making them possible candidates for investigating carcinoma with an unknown primary, particularly in cases in which PSA staining is negative and the level of suspicion is high.