The 3H-thymidine labeling index (L,I) 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 I1 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.Cancer 60:2797-2800, 1987. UTANEOUS MALIGNANT MELANOMA (MM) isC known for its resistance to most therapeutic regimens. Prognosis is related to a few morphologic parameters and influenced by different clinicopathologic features.'-' The kinetics of cell populations has been thoroughly investigated in the past 10 years in different human tumor types, and the results have important clinical implicati~ns.~-l~ However, there is little information about the proliferative activity of human MM.'.I4-I6 In our study, we proposed to define cell kinetics of human MM, to analyze them in relation to the conventional tumor and host prognostic factors, and to verify the suitability of cell kinetics as a prognostic indicator of the long-term clinical outcome in a preliminary series of Stage 11 tumor patients.Presented in part at the 1st International Conference on Skin Melanoma, Venice, May 6-9, 1985. From *Onrologia Spenmentale C, tAnatomia Patologica and Oncologia Clinica B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.Supported in part by a grant from the Associazione ltaliana per la Ricerca sul Cancro.The authors thank Miss R. Motta and L. Ventura for technical assistance.Address for reprints: A. Costa, PhD, OSC, Istituto Nazionale Tumori, Via Venezian I, 20133 Milan, Italy.Accepted for publication June 12, 1987. Patients and Methods Patient PopulationThe labeling index (LI) was determined on 178 lesions-four primary tumors and I74 metastatic lesions (79 lymph nodes, 78 subcutaneous nodules, 17 mixed material)-from 129 patients with MM. There were 49 women and 80 men. Their ages ranged from 17 to 80 years (median age, 51 years). According to the clinical classification, three patients had Stage I disease, 48 had Stage 11, and 78 had recurrent disease. Of the latter, 53 patients had been treated only with surgery, and...
SummaryThe 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.
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.
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.
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).
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