Biochemical and clinical studies have revealed a profound and selective toxic effect of elevated temperatures on tumor cells. Whereas the oxygen uptake of Novikoff hepatoma and Ehrlich ascites carcinoma cells was considerably less at 427deg;C than at 38°C, there was little difference in respiration at these two temperatures in normal and regenerating liver. The inhibition of the respiration of Novikoff hepatoma cells was irreversible after 90 min. There was no significant effect of temperature on anaerobic glycolysis. In 22 patients with cancers of the limbs the temperature in the tumors was raised to 41.5° to 43.5°C for several hours in 25 regional perfusions with prewarmed blood. Severe complications in some patients lead to six deaths and three immediate amputations. Intensive post‐treatment care was required. Three patients failed to respond; four could not be evaluated and all others had regressions. Grossly the tumors disappeared totally in ten patients, of which three recurred. Histological evaluation of multiple biopsies demonstrated complete massive necrosis in eight cases, of which none recurred, although one died and three required amputations; of these, seven are alive and free of disease. In the cases with partial regression, the tumors all recurred and required amputation or other treatment. The most responsive tumor appeared to be melanoma. No conclusions about survivals can be drawn at present although four of seven patients with malignant melanomas treated only by heat perfusion are alive and well with functional limbs 28, 27, 11 and 7 months after treatment. Only one patient has died of metastases although two have been lost to follow‐up.

These data confirm the feasibility and safety of the SLN technique for selecting patients to submit to a radical node dissection. The data represent the basis for a future trial by the WHO Melanoma Program in this field to evaluate the most appropriate surgical approach for treating patients with occult regional nodal metastases.

Mutations at the white spotting (w) locus in mice have deleterious effects on germ cells, melanocytes and hematopoietic stem cells. The w locus encodes the c-kit tyrosine-kinase receptor whose ligand is the product of the SI locus. Using monoclonal antibodies (MAb(s)) to the extracellular domain, we have evaluated the expression of c-kit in normal and transformed melanocytes. This cell lineage synthesizes a receptor with a mw of 145 kDa. The gene product is expressed in epidermal melanocytes and in a fraction of nevocytic and blue nevi. In primary melanomas, loss of the receptor is observed in more invasive lesions. Only 30% of the metastatic lesions express detectable levels of the receptor. These findings demonstrate that the c-kit product is down-regulated in melanocytes following malignant transformation. The functional relevance of this modulation remains to be evaluated.

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The cell-surface heterodimers of the integrin family of molecules, which mediate cell-cell and cell-substratum interactions, are likely to be functionally relevant in local and metastatic tumor growth. In the present study we have analyzed whether the alpha 3/beta 1 receptor for collagen, laminin and fibronectin undergoes changes in expression during tumor progression in cutaneous malignant melanoma (CMM). The results of this study have demonstrated that, while low levels of VLA3 expression are detectable in benign lesions, in primary melanomas the heterodimer undergoes progressive increase in expression which correlates with the degree of dermal invasiveness. Metastatic lesions were found VLA3 positive in 82% of cases. Furthermore, the heterodimer is homogeneously expressed in multiple autologous metastases. The presence of VLA3 correlates with detection of at least one of the ligands in 45% of the cases studied. These findings provide additional evidence that tumor progression in CMM is associated with changes in integrin phenotypes which include the alpha 3/beta 1 heterodimer.