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The prognostic role of cell kinetics (expressed as 3H-thymidine labelling index, 3H-TdR LI) was assessed on 145 patients with pathologic stage II melanoma subjected only to therapeutic lymph node dissection. The 3H-TdR LI determined on metastatic nodes was related to relapse-free survival and to survival. In particular, 3-year relapse-free survival was significantly different from patients with slowly and rapidly proliferating melanomas (40% vs 22%, P = 0.007), and this finding was consistently found for overall survival (68% vs 46%, P = 0.007). Moreover, in patients with high 3H-TdR LI tumours, the risk of relapse and death within the first year from lymphadenectomy was two-fold that of patients with low 3H-TdR LI tumours. Multiple regression analysis showed that 3H-TdR LI retained its prognostic significance on relapse-free and on overall survival even when the number of involved nodes and type of nodal metastases were considered. Present findings suggest that 3H-TdR LI can contribute to select high-risk stage II melanoma patients.

The 3H-thymidine labeling index (LI) was determined on 178 lesions, four of which were primary, from 129 patients with malignant melanoma. The overall analysis showed a wide variability of LI values, from 0.01% to 31.7%, with an exponential distribution and a median value of 8.0%. Similar median LI values were observed for the various metastatic sites, and no difference was found between patients who only had surgery and those who also received systemic therapy. Cell kinetics and patient age and sex were not related in terms of extent and type of nodal involvement. Conversely, a trend toward higher proliferative activity was observed in amelanotic (8.3%) than in melanotic (5.9%) lesions (P = 0.08). The follow-up study on a series of 48 Stage II patients has shown a higher probability of 2-year survival for patients with slowly proliferating tumors than for those with rapidly proliferating tumors (86.9% versus 40.4%, P = 0.054). Along with this finding, the absence of a relationship between cell kinetics and both the main host and tumor characteristics indicated that cell kinetics was a prognostic variable and could be an important tool in the evaluation of patients with metastatic melanoma.

Circulating levels and cyst fluid concentrations of human chorionic gonadotropin, progesterone and testosterone were measured in 30 premenopausal women with gross cystic breast disease. Specific radioimmunoassay procedures were used. Amounts of human chorionic gonadotropin exceeding 5.0 mIU/ml were found in cyst fluid of many patients, but not in serum. Progesterone and testosterone concentrations in breast cyst fluid were significantly higher than in serum (p less than 0.01 and p less than 0.001, respectively).

Six patients who developed breast cancer between the ages of 27 and 55 years had been examined for their urinary excretion of testosterone and androstanediol 17 to 69 months before the clinical onset of their cancer. Each of them showed higher than normal excretion values of testosterone or androstanediol, or both. At the time of hormonal examination, the patients were considered at risk for breast cancer because their history had included one or more of the following factors: previous mammary disease, familiality, sterility or subfertility, menstrual cycle irregularities. On the basis of this evidence, it would seem that high androgenic activity is a risk factor for developing breast cancer in patients with the "adverse" history.

An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.

Tumor cellular proliferative activity was evaluated by 3H-thymidine labeling index (LI) determination in 73 lesions from 62 patients with ovarian cancers. The median LI value for the overall series was 5.8% and places this tumor type in a position of intermediate proliferative activity. In this case series, the relationship between proliferative activity and different morphologic and pathologic characteristics of the disease was analyzed. Similar median LI values were found for ascitic effusions and solid tumors and, among these, between primary tumors and metastases. No significant relation was observed between proliferative activity and histologic type, whereas a definite direct correlation was found between the kinetic variable and prognostic features such as pathologic stage and histologic grading. In fact median LI was higher for stage IV for stage I and for grade 3 than for grade 1 tumors. The strong association between tumor proliferative rate and conventional prognostic factors suggests that also on this tumor type the kinetic variable could play a role as a prognostic indicator and modulator of aggressiveness.

Two assays based on the inhibition of 3H-thymidine incorporation into DNA were used to measure either the antimetabolic or the antiproliferative effects of anticancer drugs. A direct comparison of the two assays was made with cell suspensions obtained from 11 ovarian cancers and 22 malignant melanomas. Drugs with different effects on cell cycle phases were tested by both assays, for a total of 53 drug comparisons. When the sensitivity indices specific for each system was used, a significant association (p less than 0.01) was noted between the two assays. The agreement of both assays in defining in vitro sensitivity or resistance was 100% for ovarian cancer. For melanoma, 97% of samples resistant to the antimetabolic assay were also resistant to the antiproliferative assay; whereas, only 45% of samples sensitive to the antimetabolic assay were sensitive to the antiproliferative assay.

Urinary testosterone, androstanediol, ethiocolanolone, and androsterone glucuronide were determined by use of gas chromatography in four patients with carcinoma in situ of the breast. In all the patients, one or more of these hormones were higher than normal. This finding supports previous reports from our laboratory of increased androgen excretion in patients with fibrocystic disease or infiltrating carcinoma of the breast. Carcinoma in situ arose while the four patients were taking oral contraceptives. The progestational component of the pill, a nonderivative of testosterone, may carry with it some androgenic properties. This fact and the discovery of increased androgen excretion levels in these four patients led us to suppose that androgens could play a role in the development of breast cancer.