Quantitative estimation of tissue prostate specific antigen, deoxyribonucleic acid ploidy and cytological grade in fine needle aspiration biopsies for prognosis of hormonally treated prostatic carcinoma.

The prognostic value of deoxyribonucleic acid (DNA) flow cytometry, cytological grading and the direct assay of prostate specific antigen (PSA) in the material of fine needle aspirates was studied in 67 consecutive patients with newly detected prostatic carcinoma. All patients were hormonally treated (castration in 27 and luteinizing hormone-releasing hormone agonist or parenteral estrogens in 40). The patients were followed for a minimum of 2 years. PSA was analyzed in the biopsy material by a direct radioimmunoassay and related to the total amount of DNA. In parallel biopsies DNA ploidy using flow cytometry and cytological grade were established. Patients with a geometric mean value of greater than or equal to 0.12 microgram. PSA/microgram. DNA had a progression rate of 7%, compared to 59% for those with less than 0.12 microgram. PSA/microgram. DNA. In Cox multivariate analysis cytology and tissue PSA content were the most important factors in expressing the difference for interval to progression in hormonally treated patients.

Deoxyribonucleic acid ploidy and the direct assay of prostatic acid phosphatase and prostate specific antigen in fine needle aspiration biopsies as diagnostic methods in prostatic carcinoma.

We used fine needle biopsies from prostatic tumors at routine examinations in 133 patients. Cytological grading was performed with a scoring system. Cellular prostatic acid phosphatase and cellular prostate specific antigen from the aspirates were quantitated. Deoxyribonucleic acid flow cytometry was performed and the tumors were subdivided into diploid, tetraploid and aneuploid groups. Tumor staging was assessed by digital examination. A decrease in the biochemical markers was significantly correlated with the increase in malignancy grade, tumor stage and a shift from diploid to aneuploid tumors. Cellular prostatic acid phosphatase and cellular prostate specific antigen as well as tumor ploidy may contribute to the objective determination of the malignancy potential of the prostatic carcinoma.

PAP and PSA in prostatic carcinoma cell lines and aspiration biopsies: relation to hormone sensitivity and to cytological grading.

Because a change from hormone-sensitive to hormone-resistant carcinoma of the prostate often occurs concomitantly with genetic changes or as a result of the latter, the markers specific for prostatic tissues might also be affected. We therefore first studied the presence of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in LNCaP and LNCaP-r human prostatic carcinoma cell lines. Since both markers were found in these cell lines, we proceeded to quantitate PAP and PSA in aspiration biopsies from patients with prostate tumors. The amounts of these markers were compared with cytological findings. PAP and PSA were analyzed in the biopsy material from 120 patients using commercial radioimmunoassay (RIA) kits. DNA was determined using Riedel H33258 stain. Cytological grading was performed according to the Uropathological Study Group of Prostatic Carcinoma. Significant correlations were found between PAP/DNA or PSA/DNA values and grade of differentiation of the prostate tumor. In view of earlier reports and the results presented here, the amounts of markers or the protein pattern of tumor tissue may be a useful complement to the morphological findings and for selecting optimal therapy for patients with prostatic tumors.

The human prostatic carcinoma cell line LNCaP and its derivatives. An overview.

The FGC (fast growing colony) line, a derivative of the LNCaP cell line shares all the main characteristics, including its androgen dependence, described for the original LNCaP cultures. A number of sublines originated from the FGC line which were characterized with respect to their response to steroid-depleted serum and to the synthetic androgen, R1881. After subcloning the FGC line a series of clones was isolated with distinct patterns of androgen-responsiveness. Among the sublines and clones studied, the FGC, FGC-JB and FGC clone-9 were androgen-dependent, whereas subline LNO, R and presumably also FGC clone-22 were androgen-independent. Distinct morphological differences were observed between the cells of the various sublines and between clone-9 and 22. The LNCaP cell line, its descending sublines and clonal derivatives provide a suitable in vitro model for studying different aspects of androgen-responsiveness of human prostate cancer.

Difference in uptake of 3H-estramustine in two human prostatic carcinoma cell lines, LNCaP and LNCaP-r.

Estramustine, estradiol-3-N-bis(2-chloroethyl)carbamate (EM), has been shown to inhibit growth of the human prostatic carcinoma cell line LNCaP as well as its subline LNCaP-r. The hormone sensitive LNCaP showed greater sensitivity to the drug than the hormoneresistant LNCaP-r. LNCaP has also shown an increasing sensitivity to 10(-7) M EM, when incubated with different concentrations of steroid hormones. We studied whether the increasing sensitivity was caused by increased uptake of EM. 3H-estramustine was added to medium and the cells were incubated 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, and 4 h, or 2 h, 4 h, 6 h, and 8 h. No effect of steroids on the uptake of EM was noted, but LNCaP showed a higher uptake of EM compared to LNCaP-r. The uptake of EM in LNCaP increased for eight hours, whereas LNCaP-r reached its maximum uptake after six hours of incubation.

Effect of hormones on growth and ATP content of a human prostatic carcinoma cell line, LNCaP-r.

The use of ATP content as a measurement for cell growth was evaluated in the LNCaP prostatic cancer cell line. ATP content was found to correlate well with cell counts and was an easy and reliable method for following the effect of substances on cell growth. During cultivation for 9 days no effect on cell counts or ATP content could be seen when testosterone (10(-10) to 10(-6) M), estradiol-17 beta (10(-10) to 10(-5) M), 5 alpha-DHT (10(-9) to 10(-6) M), prolactin, vitamin A, or antiandrogen was added to the cell medium in different combinations. However, a weak positive effect was seen on the mitotic index when 10 or 100 nM 5 alpha-DHT was added to the cells, whereas 1 microM 5 alpha-DHT inhibited cell growth. Thus despite the fact that this LNCaP line contained 16 fmol androgen receptor/mg protein (Kd 0.6 nM), it is unresponsive to hormones and should be designated LNCaP-r (resistant). Chromosome analysis revealed that a shift in the modal chromosome number had occurred from the original LNCaP line, which could account for the lack of hormonal sensitivity.