Pre-treatment DNA ploidy of sperm cells as a predictive parameter of post-treatment spermatogenesis in patients with testicular cancer.

OBJECTIVE: To evaluate DNA flow cytometry (DNA FCM) as a means of predicting post-treatment spermatogenesis in patients with testicular cancer. SUBJECTS AND METHODS: After unilateral orchidectomy and before further treatment (pre-treatment), light microscopic sperm cell analysis and FCM were performed in 96 patients in whom post-treatment sperm cell counts were available > or = 2 years after therapy. Twenty-nine patients had not received any cytotoxic treatment after orchidectomy, whereas 64 had received either abdominal radiotherapy [37] or 3-4 cycles of cisplatin-based chemotherapy [27]. Three patients had both chemotherapy and radiotherapy. A control group consisted of 26 healthy age-matched men. RESULTS: In the pre-treatment situation 43% of the patients had low sperm counts (< 10 x 10(6)/ml). A median of 38 months after treatment the median sperm cell density had increased significantly, independent of treatment, but was still less than that of the control group. All control specimens, but only 66% of the patients' ejaculates, contained cells of which more than 90% were classified as being condensed DNA haploid sperm cells. The median percentages of cells classified as non-condensed DNA haploid, as DNA diploid or as being above DNA diploid cells were increased in the patients' samples as compared with those of the controls, both before and after treatment. CONCLUSION: Spermatogenesis is quantitatively and qualitatively impaired in patients with newly diagnosed testicular cancer. Long-term recovery is relatively independent of routine treatment but is related to the pre-treatment sperm cell density. For the whole series of patients DNA FCM parameters did not yield independent parameters which predicted recovery of spermatogenesis. In patients in whom no sperm cells were found by light microscopy of the seminal fluid the demonstration of > or = 30% condensed DNA haploid cells was correlated with post-treatment recovery of spermatogenesis.

Clinical significance of DNA ploidy and S-phase fraction and their relation to p53 protein, c-erbB-2 protein and HCG in operable muscle-invasive bladder cancer.

DNA ploidy and S-phase fraction (SPF), determined by flow cytometry were studied in 118 patients with muscle-invasive transitional cell carcinoma (TCC) of the urinary bladder, scheduled for cystectomy after pre-operative radiotherapy (20 Gy/1 week) with or without systemic cisplatin-based neo-adjuvant chemotherapy. The correlation between these parameters and immunohistochemically demonstrated p53, c-erbB-2 and HCG was also investigated. There were 16 DNA diploid and 102 DNA non-diploid tumours. DNA ploidy was not related to the T (all 118 patients) or pN (58 patients) category, occurrence of stage reduction or cancer-related 5 years survival. Patients with high SPF tumours tended, however, to have a better prognosis than those with low SPF TCC reaching the level of significance (P < 0.05) for those patients who had high SPF tumours and received neo-adjuvant chemotherapy. Fifty-one of the tumours were p53 positive. p53 positive tumours were significantly more often found in TCC with low SPFs than in those with high SPFs. Respectively 12 and 9% of the tumours were HCG and c-erbB-2 positive, without correlation to DNA ploidy or SPF. We conclude that DNA ploidy does not represent a prognostic parameter in muscle-invasive operable bladder carcinomas. A high SPF, determined by FCM, may be helpful to identify patients with chemotherapy-sensitive TCC of the urinary bladder.

Hormone resistant prostatic adenocarcinoma. An evaluation of prognostic factors in pre- and post-treatment specimens.

Pre- and post-treatment specimens from 47 patients with hormone resistant prostatic carcinoma were compared with each other regarding histological grade and immunoreactivity for p53 protein, neuron specific enolase and c-erbB-2 protein. Significantly more specimens expressed a high malignancy grade when the tumour had become hormone resistant than at the time of initial diagnosis (Gleason P: < 0.0001, WHO P:0.0003). p53 protein immunoreactivity increased significantly with disease progression (P:0.006), while tissue PSA immunoreactivity was reduced in post-treatment specimens (P:0.011). p53 protein expression did not correlate with histological grade or PSA expression and seems to be an independent parameter which participates late in the neoplastic transformation. Thirty-two percent of the tumours were neuron specific enolase positive, but this parameter did not correlate with development of hormone resistance. c-erbB-2 protein reactivity was not recognised.