Changes in immunohistochemical staining of PSA, PAP, and TURP-27 following irradiation therapy for clinically localized prostate cancer.

OBJECTIVES: To determine if tissue expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and a prostate-associated monoclonal antibody (TURP-27) is retained after irradiation therapy and to compare these results with serum levels. METHODS: Immunohistochemical tests were performed on prostatic tissue obtained by needle biopsy or transurethral resection prior to and following definitive irradiation therapy for clinically localized prostatic carcinoma. PSA, PAP, and TURP-27 were studied. Results were compared with serum PSA and PAP values. RESULTS: All 20 preirradiation specimens stained positively for PSA and PAP; 19 of 20 stained for TURP-27. All 5 of the initial post-treatment biopsy specimens that showed recurrent tumor stained for all 3 markers. In 2 cases, staining for the 3 markers was greatly diminished. Only 8 of 15 post-treatment biopsy-negative specimens stained for all 3 markers. Six of 15 demonstrated loss of tissue expression for all 3 antigens. One specimen stained for PAP and TURP-27 but failed to stain for PSA. Serum PSA levels paralleled tissue expression in recurrent tumor specimens. However, 3 of the post-treatment biopsy-positive cases with PAP expressing tissue had normal serum PAP levels. CONCLUSIONS: No cases of recurrent tumor with marker-negative tissue were identified. However, benign epithelial prostate cells appear to sustain sufficient damage from irradiation to lose the capacity to produce certain proteins. Diminished contribution of benign glands to circulating PSA, in addition to decreased expression in malignant tissues, may explain the lower than anticipated serum PSA levels in patients who progress after irradiation therapy.

Prostate specific antigen levels after definitive irradiation for carcinoma of the prostate.

Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined.

Comparison of countercurrent immunoelectrophoretic assay with commercial radioimmunoassay kits for measuring prostatic acid phosphatase.

We evaluated and compared five commercial radioimmunoassay kits with a standard counter-immunoelectrophoretic assay for the measurement of prostatic acid phosphatase in serum. Four of the five radioimmunoassays performed as described by the supplier with respect to sensitivity, stability, precision, linearity, analytical recovery, and expected values for the normal male population. None of the radioimmunoassays was more clinically sensitive then the counter-immunoelectrophoretic assay for detecting increased prostatic acid phosphatase in serum. Results obtained by counter-immunoelectrophoretic assay agreed with results obtained by radioimmunoassay in 96% of the tests. The proportion of positive results in patients with confirmed prostatic adenocarcinoma increased with disease progression. The fewer positive tests in localized adenocarcinoma (Stages A and B) suggests that neither the counter-immunoelectrophoretic assay nor the radioimmunoassay procedures are useful for screening unselected populations for adenocarcinoma of the prostate. The high percentage of normal values found in those patients clinically free of disease after treatment is encouraging and supports the use of the prostatic acid phosphatase immunoassays in prospectively monitoring the treatment of prostatic cancer patients.

Leukocyte migration inhibition assay in patients with prostate adenocarcinoma.

The leukocyte migration inhibition (LMI) assay was used to determine the cell-mediated immune reactivity of prostate cancer patients to putative tumor antigens present in potassium chloride extracts of surgically removed prostate tumor tissue. Using an extract prepared from prostate tumor tissue, inhibition of leukocyte migration was found more frequently in prostate tumor patients (61%) than in patients with benign prostate hyperplasia (37%), patients with nonprostate cancers (26%), or normal donors (10%). Control extracts prepared from normal prostate tissue, benign prostate hyperplasia tissue, and unrelated tumor tissue were statistically less reactive in the LMI assay than the prostate tumor extract when reacted against leukocytes from prostate tumor patients. These results suggest that the LMI assay might be potentially useful for measuring the tumor-directed, cell-mediated immune responses in patients with prostate cancer.